LL-37: the body's own antibiotic, and its double life in the skin
LL-37 is the only human cathelicidin, a 37-amino-acid peptide that kills microbes, steers immune cells and is switched on by vitamin D. It also helps drive psoriasis and rosacea.
At a glance
- LL-37 is the only cathelicidin antimicrobial peptide in humans. It is 37 amino acids long and is cut from a precursor protein, hCAP18, made from the CAMP gene [1,2].
- It kills bacteria by disrupting their membranes and also acts as an immune signal, attracting cells and helping skin wounds close [3,5].
- Vitamin D switches the gene on through a control element that exists in primates but not in mice, rats or dogs [6,7].
- In skin it cuts both ways: missing from the edges of chronic ulcers [5], but overactive or wrongly processed in psoriasis and rosacea [8-10].
- Topical LL-37 has reached randomised trials for leg ulcers. A 34-person early trial looked promising; a 148-person phase 2b missed its main goal [11,12].
- Not approved as a medicine anywhere [12,14].
A missing peptide and a clue
People with Kostmann syndrome are born with a severe lack of neutrophils, the white blood cells that fight bacteria. A growth-factor drug restores their neutrophil counts, yet they still suffer repeated infections and gum disease [4].
In 2002, researchers looked for the reason. They found that these patients' neutrophils lacked the precursor of LL-37, and that the precursor was undetectable in their saliva and plasma [4]. One patient who had received a bone-marrow transplant had near-normal LL-37 levels and normal gums [4]. It was a small study, six patients, but a vivid hint of how much one peptide might matter.
LL-37 has since become one of the most studied human antimicrobial peptides, partly as a model for new antibiotics and partly because it turns up in so many diseases.
Origin: from a bone-marrow library to the neutrophil
The peptide was first predicted in the mid-1990s from a gene sequence found in a human bone-marrow library, as a 39-residue form called FALL-39 [1]. In 1996, the same group sequenced the full gene and showed that it is the only member of the cathelicidin family in the human genome [1]. When they isolated the mature peptide from activated granulocytes, it turned out to be 37 residues long and to start with two leucines: LL-37 [1].
Inside neutrophils the peptide is stored as the inactive precursor hCAP18. It is only cut free after the cell releases its granules, by an enzyme called proteinase 3 [2]. LL-37 is also made by epithelial cells of the skin, gut, airways and testis, and by several kinds of white blood cell [3].
How it works: a membrane breaker that also sends signals
LL-37 folds into a helix with a positively charged face and a fat-loving face [3]. Bacterial membranes carry a strong negative charge, so the peptide is drawn to them and then disrupts them, which gives it broad activity against many microbes [3].
Picture a magnet attached to a crowbar. The charge pulls LL-37 onto the bacterial surface; the helix then pries the membrane apart. Human cell membranes carry less negative charge, which gives some selectivity [3], but LL-37 can also be toxic to human cells [2].
Killing is only part of the job. LL-37 attracts immune cells to infection and wound sites, neutralises bacterial endotoxin (LPS) and promotes the closure of wounds [3].
The vitamin D connection
The CAMP gene's promoter contains a vitamin D response element, so the active form of vitamin D strongly switches the gene on in immune cells, bone-marrow cells and skin and colon cell lines [6]. That element sits inside a stretch of DNA found only in primates; mice, rats and dogs lack it [6]. This is one reason mouse studies say little about vitamin D and cathelicidin in people.
In 2006, a study in Science tied this to tuberculosis. Activating immune sensors on human macrophages raised their vitamin D receptor and vitamin D-activating enzyme, induced cathelicidin, and helped kill Mycobacterium tuberculosis [7]. Serum from people with low vitamin D levels supported this response poorly [7].
What the research shows
Wound healing
In human skin, levels of hCAP18 rise sharply after wounding, peaking at about 48 hours, and fall back as the wound closes [5]. In chronic leg ulcers, by contrast, the peptide is absent from the epithelium at the ulcer edge [5]. In cultured human skin, antibodies that block LL-37 slowed wound closure [5].
Psoriasis: when the defender becomes the trigger
In psoriasis, LL-37 turns the body's own DNA into an alarm signal, and in about two-thirds of moderate-to-severe cases it becomes a target of the immune system itself [8,9].
LL-37 is overproduced in psoriatic skin. In 2007, researchers showed that it binds fragments of the body's own DNA and carries them into plasmacytoid dendritic cells, which then mistake them for viral DNA and release interferon [8]. In 2014, a team including some of the same researchers found that about two-thirds of patients with moderate-to-severe plaque psoriasis carried T cells that specifically recognise LL-37, and that their presence tracked disease activity [9].
Rosacea
People with rosacea have unusually high levels of cathelicidin in facial skin, and it is chopped into abnormal fragments by an overactive skin protease [10]. Injecting these rosacea-type fragments into mouse skin caused inflammation, and mice lacking the cathelicidin gene were protected [10].
Clinical trials of topical LL-37
| Trial | Patients | Design | Main result |
|---|---|---|---|
| Venous leg ulcers, first-in-human (2014) [11] | 34 | Randomised, double-blind, 4 weeks, three strengths vs placebo | Faster healing at the lowest strength, a trend at the middle one, no benefit at the highest; no safety concerns |
| HEAL LL-37, venous leg ulcers, phase 2b (2021) [12] | 148 | Randomised, double-blind, two strengths vs placebo, with compression | No significant improvement overall; post hoc benefit in large ulcers |
| Diabetic foot ulcers (2023) [13] | 25 | Randomised, double-blind, 4 weeks vs placebo cream | Better granulation tissue; no significant difference in wound area |
In the first trial, the healing rate in the 0.5 mg/mL arm was about six times that of placebo, but the 3.2 mg/mL arm did no better than placebo [11]. The larger phase 2b, run by the developer Promore Pharma, which calls the drug ropocamptide, did not confirm a benefit across all patients [12]. Its positive finding in ulcers of at least 10 cm² came from an analysis planned after the fact, which needs a new trial to test [12].
What we don't know yet
Whether it heals wounds in people. The largest trial missed its primary endpoint [12]. The diabetic-foot result rests on 25 patients and a surrogate measure [13].
Why lower strengths worked better. In the first trial the highest concentration lost the effect [11], which is unexplained.
Whether more is better, or worse. The same peptide that may help wounds feeds inflammation in psoriasis and rosacea [8-10]. How added LL-37 behaves in people with these conditions has not been studied.
Safety beyond the skin. Human trials have used topical application only [11-13]. FDA notes that nonclinical studies suggest LL-37 may promote tumours in some tissues and may harm male reproduction [14].
Regulatory status
- Approval: LL-37 is not approved as a medicine anywhere. As of the 2021 phase 2b report, Promore Pharma was developing it for leg ulcers as ropocamptide [12].
- FDA, 2023: Placed "cathelicidin LL-37" in Category 2 on 29 September 2023, citing immunogenicity risk, impurity and characterisation problems, insufficient safety information and nonclinical signals of tumour promotion and reproductive harm [14].
- FDA, 2026: After the nomination was withdrawn, LL-37 was moved to the "nominated but withdrawn" list by April 2026 [14].
- WADA: LL-37 is not named on the Prohibited List, but anti-doping agencies treat non-approved peptides as falling under class S0 [15].
In the lab: handling and storage
LL-37 is supplied as a lyophilised powder. Standard practice for research peptides applies: −20 °C for long-term storage, 2-8 °C for short periods, and protection from light and moisture. Reconstituted solutions are usually refrigerated, used within a short window and not repeatedly frozen and thawed. At 37 residues it is a long peptide for chemical synthesis, and FDA lists impurities and characterisation as specific concerns [14], so the certificate of analysis should confirm identity by mass spectrometry (about 4,493 Da) and purity by HPLC.
FAQ
What is LL-37?
Does vitamin D increase LL-37?
Is LL-37 linked to psoriasis and rosacea?
Has LL-37 been tested in humans?
How Synthos supplies LL-37
Every Synthos lot of LL-37 is tested by an independent laboratory, and the certificate of analysis for that lot comes with your order. Ask your representative to see it before you pay anything.
Further reading elsewhere
Coverage and explainers from other publications, picked and checked by our team.
- US FDA · Apr 2026Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks ↗FDA's list of compounding safety concerns, including its notes on cathelicidin LL-37.
- Medsafe (New Zealand) · Jun 2025Classification of Unscheduled Peptides: Submission to the Medicines Classification Committee ↗New Zealand's regulator recommends classing antimicrobial peptides such as LL-37 as prescription medicines.
- Nature (News & Views) · Oct 2007Skin deep but complex ↗Explains the discovery that LL-37 lets immune cells mistake the body's own DNA for a threat in psoriasis.
- Nature Medicine (News & Views) · Aug 2007Rosacea: skin innate immunity gone awry? ↗Commentary on the finding that abnormal cathelicidin processing drives skin inflammation in rosacea.
References
- Gudmundsson GH, Agerberth B, Odeberg J, Bergman T, Olsson B, Salcedo R. The human gene FALL39 and processing of the cathelin precursor to the antibacterial peptide LL-37 in granulocytes. Eur J Biochem. 1996;238(2):325-332. PubMed
- Sørensen OE, Follin P, Johnsen AH, et al. Human cathelicidin, hCAP-18, is processed to the antimicrobial peptide LL-37 by extracellular cleavage with proteinase 3. Blood. 2001;97(12):3951-3959. PubMed
- Dürr UH, Sudheendra US, Ramamoorthy A. LL-37, the only human member of the cathelicidin family of antimicrobial peptides. Biochim Biophys Acta. 2006;1758(9):1408-1425. PubMed
- Pütsep K, Carlsson G, Boman HG, Andersson M. Deficiency of antibacterial peptides in patients with morbus Kostmann: an observation study. Lancet. 2002;360(9340):1144-1149. PubMed
- Heilborn JD, Nilsson MF, Kratz G, et al. The cathelicidin anti-microbial peptide LL-37 is involved in re-epithelialization of human skin wounds and is lacking in chronic ulcer epithelium. J Invest Dermatol. 2003;120(3):379-389. PubMed
- Gombart AF, Borregaard N, Koeffler HP. Human cathelicidin antimicrobial peptide (CAMP) gene is a direct target of the vitamin D receptor and is strongly up-regulated in myeloid cells by 1,25-dihydroxyvitamin D3. FASEB J. 2005;19(9):1067-1077. PubMed
- Liu PT, Stenger S, Li H, et al. Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science. 2006;311(5768):1770-1773. PubMed
- Lande R, Gregorio J, Facchinetti V, et al. Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide. Nature. 2007;449(7162):564-569. PubMed
- Lande R, Botti E, Jandus C, et al. The antimicrobial peptide LL37 is a T-cell autoantigen in psoriasis. Nat Commun. 2014;5:5621. PubMed
- Yamasaki K, Di Nardo A, Bardan A, et al. Increased serine protease activity and cathelicidin promotes skin inflammation in rosacea. Nat Med. 2007;13(8):975-980. PubMed
- Grönberg A, Mahlapuu M, Ståhle M, Whately-Smith C, Rollman O. Treatment with LL-37 is safe and effective in enhancing healing of hard-to-heal venous leg ulcers: a randomized, placebo-controlled clinical trial. Wound Repair Regen. 2014;22(5):613-621. PubMed
- Mahlapuu M, Sidorowicz A, Mikosinski J, et al. Evaluation of LL-37 in healing of hard-to-heal venous leg ulcers: a multicentric prospective randomized placebo-controlled clinical trial. Wound Repair Regen. 2021;29(6):938-950. PubMed
- Miranda E, Bramono K, Yunir E, et al. Efficacy of LL-37 cream in enhancing healing of diabetic foot ulcer: a randomized double-blind controlled trial. Arch Dermatol Res. 2023;315(9):2623-2633. PubMed
- US Food and Drug Administration. Certain bulk drug substances for use in compounding that may present significant safety risks. Content current as of 22 April 2026 (earlier versions list cathelicidin LL-37 as added to Category 2 on 29 September 2023). FDA
- Sport Integrity Canada. Reminder: non-approved peptides included on the Prohibited List. 27 April 2026. Sport Integrity Canada
This article summarises published research for education and laboratory context. It is not medical advice. Synthos products are sold for laboratory research only and are not approved for human use.