What is LL-37 in Antimicrobial and Immune Research?

LL-37 Peptide: The Human Cathelicidin in Antimicrobial and Immune Research

LL-37 is the only human cathelicidin antimicrobial peptide, a 37-residue cationic peptide that both punctures microbial membranes and signals to the immune system. This research-use-only reference explains how LL-37 kills microbes, recruits immune cells through the FPR2 receptor, neutralizes bacterial endotoxin, and behaves differently at low versus high concentrations.

Michael Phelps

Founder & Peptide Research Specialist, PrymaLab

Research reference · Last updated July 23, 2026 · ~9 min read

What Is LL-37?

LL-37 is the single human member of the cathelicidin family of antimicrobial peptides. It is a 37-amino-acid cationic peptide (its name comes from the two leucines at the start and its length) released by proteolytic cleavage from the C-terminus of the hCAP18 protein, the product of the CAMP gene. It is produced by neutrophils, epithelial cells of skin and mucosa, and other immune cells, placing it at the front line of innate defense.^[1]

How LL-37 folds

LL-37 has no fixed shape in dilute water. Johansson and colleagues found that at micromolar concentration in water it gave a circular dichroism spectrum consistent with a disordered structure, and that 15 mM bicarbonate, sulfate or trifluoroacetate turned it helical with roughly equal efficiency, while 160 mM chloride was less effective (Johansson et al. 1998). Helicity rose cooperatively with peptide concentration, which the authors read as oligomer formation. Below pH 5 the helix content fell gradually, and at pH 2 the peptide was entirely disordered, while the helix survived above pH 13 (Johansson et al. 1998). The degree of helicity correlated with antibacterial activity against Gram-positive and Gram-negative bacteria, and two N-terminally shortened forms, FF-33 and SK-29, needed more anion to fold and were less active against E. coli (Johansson et al. 1998). In solutions matching plasma or interstitial fluid LL-37 was helical, yet human serum inhibited both its antibacterial and its cytotoxic activity (Johansson et al. 1998).

Wang's 2008 NMR structure showed the folded peptide against a membrane-like surface. In SDS micelles LL-37 formed a curved amphipathic helix-bend-helix spanning residues 2 to 31, bent between Gly-14 and Glu-16, with a disordered C-terminal tail; phenylalanines 5, 6, 17 and 27 and the arginines made direct contact with anionic lipid micelles (Wang 2008). Working with synthetic fragments, Wang identified KR-12, residues 18 to 29, as the smallest antibacterial peptide, selectively toxic to bacteria and not to human cells (Wang 2008).

How Does LL-37 Kill Microbes?

LL-37 is cationic and amphipathic, so it is drawn to the negatively charged surface of bacterial membranes and inserts into them, breaking membrane integrity. Because this is a physical, membrane-level mechanism rather than a single enzyme target, classical resistance is harder for microbes to develop.^[2] In research models it shows activity against Gram-positive and Gram-negative bacteria and some fungi and viruses.

Why it draws interest: a host-derived, membrane-active peptide is studied as a template for antimicrobial approaches where conventional antibiotics are losing ground.^[3]

How Does LL-37 Modulate the Immune System?

LL-37 does more than kill. It recruits neutrophils, monocytes, and CD4+ T cells to sites of infection and injury by acting on the formyl peptide receptor FPR2 (also called FPRL1), and it promotes angiogenesis through FPR2-linked VEGF signaling.^[1] That dual identity, direct antimicrobial plus immune messenger, is why LL-37 is studied as a "host defense peptide" rather than only an antibiotic.

How Does LL-37 Neutralize LPS (Endotoxin)?

LL-37 binds bacterial lipopolysaccharide (LPS, the endotoxin on Gram-negative bacteria) with high affinity. By sequestering LPS, it reduces LPS activation of TLR4 on macrophages and blunts the pro-inflammatory cytokine cascade that can drive sepsis in models.^[1] This endotoxin-neutralizing property is a distinct research angle from its direct microbial killing.

Is LL-37 Anti-Inflammatory or Pro-Inflammatory?

Both, depending on concentration, which is the honest and important nuance. At low concentrations LL-37 tends to be anti-inflammatory, suppressing TNF-alpha release from LPS-stimulated macrophages. At high concentrations it can become pro-inflammatory.^[1] Context (cell type, local level, other signals) shapes the outcome, so results do not reduce to a single "LL-37 is anti-inflammatory" claim.

What Does LL-37 Do in Wound-Healing Models?

In tissue-repair research, LL-37 is linked to faster wound closure through several routes at once: it promotes angiogenesis, stimulates the migration of keratinocytes and other cells, and is associated with collagen deposition.^[3] These are model-based observations, and how they translate to controlled human outcomes remains an open, actively studied question.

LL-37 in cancer research

The cancer literature on LL-37 points in two directions. A 2010 review by Wu and colleagues described overexpression of LL-37 as implicated in the development or progression of several human cancers, including breast, ovarian and lung cancer, while in gastric cancer it suppressed tumorigenesis; the authors wrote that the reasons for this tissue-specific behaviour remained to be explained (Wu et al. 2010).

The breast cancer work is the most detailed. Weber and colleagues measured hCAP18 mRNA in 109 primary breast cancers and found that it correlated closely with ERBB2 expression and, in oestrogen receptor-positive tumours, with lymph node metastases (Weber et al. 2009). In cell lines, hCAP18 and LL-37 amplified heregulin-induced MAPK signalling through ErbB2, and LL-37 stimulated cancer cell migration and gave colonies in soft agar a dispersed shape associated with metastatic potential (Weber et al. 2009). A truncated version of LL-37 competitively inhibited these effects (Weber et al. 2009). In SCID mice, transgenic overexpression of hCAP18 in a breast cancer cell line of low malignancy promoted metastases, and the authors concluded that hCAP18 and LL-37 contribute to breast cancer metastasis (Weber et al. 2009).

These findings come from tumour samples, cell lines and immunodeficient mice. They sit alongside the angiogenesis and wound-repair work described above, which is a reason to read claims that LL-37 promotes tissue growth with the tumour data in mind.

How is research-grade LL-37 characterized?

LL-37 is a long, cationic peptide, so identity and purity verification matter for reproducible immunology and antimicrobial work. Research-grade LL-37 is typically confirmed by reversed-phase HPLC for purity and mass spectrometry for identity, handled cold, and supplied for laboratory use only. At PrymaLab, every lot is tested in its own laboratory (RP-HPLC purity, LC-MS identity), and certificates can be checked at prymalab.net/testing/verify. Under PrymaLab's third-party testing guarantee, if any independent laboratory finds the wrong compound or less than the stated purity or amount, the order is refunded and the test reimbursed. No specific lot data are asserted in this general reference.

Frequently Asked Questions

What is LL-37?

The only human cathelicidin antimicrobial peptide, a 37-residue cationic peptide cleaved from hCAP18 (CAMP gene), produced by epithelial and immune cells.

How does LL-37 work?

It disrupts microbial membranes directly and, separately, signals through FPR2 to recruit immune cells, drives angiogenesis, and binds LPS to reduce TLR4-driven inflammation.

Is LL-37 anti-inflammatory?

At low concentrations it tends to be anti-inflammatory; at high concentrations it can be pro-inflammatory. The effect is concentration- and context-dependent.

Is LL-37 approved for human use?

No. LL-37 reference material is for laboratory research only and is not a drug or treatment.

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