LL-37 (Cathelicidin)

What Is LL-37?

LL-37 is the only cathelicidin antimicrobial peptide made by humans, a 37-residue host-defense peptide produced mainly by phagocytic leukocytes and epithelial cells. It was discovered in human neutrophils and is known for broad-spectrum antimicrobial activity and immunomodulatory functions.^[1]

LL-37 is the C-terminal peptide of the human cathelicidin antimicrobial protein, called CAMP or hCAP18.^[2] Once released from this precursor, it can act directly on microorganisms by inserting into their surface structures and can also act as an agonist at several host cell membrane receptors.^[3]

A 2016 review called hCAP18/LL-37 a paradigm for the many roles of peptides in host defense. Its reported activities include killing microbes, acting as an alarmin that helps coordinate the immune response, raising or limiting local inflammation, and promoting angiogenesis and wound healing.^[4]

Chemical Structure and Molecular Identity

LL-37 is a linear 37-amino-acid peptide, LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES, with free N- and C-termini. PubChem lists it under CID 16198951 with the molecular formula C205H340N60O53 and a molecular weight of 4493 g/mol. Its CAS number is 154947-66-7, and its international nonproprietary name is ropocamptide.

The name reflects the two N-terminal leucine residues and the 37-residue length. The sequence carries six lysines and five arginines against three glutamates and two aspartates, giving a net charge of about +6 at neutral pH. This positive charge is consistent with its description as a cationic peptide.^[5]

LL-37 performs its activities with a small, simple, amphipathic helical structure. It tends to form oligomers under physiological solution conditions and to bind molecular surfaces as an oligomer, which a 2016 review links to some of its cytotoxic and immunomodulatory effects.^[4]

As an unmodified linear peptide, LL-37 is sensitive to proteolysis. Reviews identify this proteolytic sensitivity, along with potential toxicity at high concentrations, as a key obstacle to therapeutic development.^[6]

Research History and Development

LL-37 was first studied as an antimicrobial molecule from neutrophils and later recognized as a multifunctional immune regulator. A 2024 study summarized this shift: initially investigated for its antimicrobial role, LL-37 was found to have pleiotropic activities such as immunomodulation, angiogenesis stimulation and tissue healing.^[5]

Research has since spread into many fields. Reviews published from 2018 to 2026 cover its roles in cancer, oral health and periodontitis, heart disease, sepsis, atopic dermatitis and wound healing.^{[2][3][7][8][9][10]} Its expression has also been tied to vitamin D: vitamin D-dependent induction of cathelicidin in human macrophages has been reported to activate anticancer activity of tumor-associated macrophages.^[2]

Development work has moved toward derivatives that address the parent peptide’s weaknesses. Engineered LL-37-related peptides have been designed for heart disease research,^[7] and ceragenins, non-peptide synthetic mimics resistant to proteolysis, are being studied alongside LL-37 in wound healing.^[10] Reviews of sepsis and antimicrobial research both call for stable LL-37 analogs.^[8][6]

Mechanisms Studied in Research

LL-37 acts on microbes mainly by disrupting their membranes and on host cells mainly through membrane receptors and signaling pathways. A 2016 review describes it as a pore-forming toxin directed against bacterial cells, with separate membrane-dependent effects on human cells that underlie many of its other host-defense activities.^[4]

Antimicrobial and antibiofilm mechanisms

Against biofilms, reported mechanisms include inhibition of bacterial adhesion, downregulation of biofilm-associated genes, suppression of quorum-sensing pathways, degradation of biofilm matrix and killing of biofilm-residing cells.^[11] Against fungi, studies describe cell wall damage, membrane permeabilization, oxidative stress, endoplasmic reticulum disruption and cell cycle inhibition.^[12] Antiviral mechanisms reported in the literature include disruption of viral envelopes and interference with viral entry and replication.^[6]

Immune signaling

LL-37 forms complexes with nucleic acids that are immunostimulatory. Some studies suggest these LL-37/nucleic acid complexes may contribute to autoimmune conditions such as psoriasis and systemic lupus erythematosus.^[13] In cancer, different membrane receptors on different cancer cells appear to explain tissue-specific effects.^[2]

Barrier function

In skin, LL-37, human beta-defensins and S100A7 have been reported to improve tight junction barrier function.^[9] In intestinal cell lines, LL-37 protected goblet cells by increasing transepithelial resistance and mucin-2 and Nrf2 expression.^[14]

Key Findings From Published Studies

Most published evidence on LL-37 comes from in-vitro antimicrobial assays, animal models and measurements of natural LL-37 in human tissue, rather than trials of the peptide in people. The main findings by evidence type are summarized below.

In-vitro antimicrobial activity

A 2025 review of standardized tests reported activity against more than 38 bacteria, 16 fungi and 16 viruses.^[6] LL-37 prevented biofilm establishment by pathogens including Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae and Acinetobacter baumannii,^[11] and inhibited fungi including Aspergillus, Candida, Fusarium and Trichophyton.^[12]

Animal models

In a rat heat stroke model, LL-37 reduced intestinal injury, systemic inflammation and nitrosative stress, and improved organ dysfunction, coagulopathy and survival.^[14] A 2025 sepsis review reports that exogenous LL-37 increased survival in mice with experimentally induced sepsis.^[8]

Human tissue and observational data

• Breast implant capsules: in 29 capsules from 28 women, LL-37 was expressed by macrophages in 34% and myofibroblasts in 31% of specimens; macrophage expression negatively correlated with contracture severity (P = 0.04).^[5]
• Periodontitis: several studies found higher LL-37 levels in gingival crevicular fluid of patients than in healthy controls.^[1]
• Inflammatory bowel disease: high cathelicidin expression in ileal samples was associated with better clinical outcome.^[14]
• Sepsis: LL-37 blood concentrations change markedly during sepsis.^[8]

Cancer: opposite effects by tissue

LL-37 has been reported to promote tumors of the ovary, lung, breast, prostate and pancreas, malignant melanoma and skin squamous cell carcinoma, but to have anticancer effects in colon, gastric, hematologic and oral squamous cell cancers.^[2] This dual behavior, and its possible role in autoimmunity, is one reason reviewers say questions about in-vivo efficacy and safety remain unanswered.^[11]

Other research areas

Reviews also link LL-37 to the regulation of atherosclerosis, thrombosis, inflammatory responses and cardiac hypertrophy.^[7] In wound-healing research, it is reported to support cell migration and proliferation in addition to preventing infection.^[10] In the mouth, oral LL-37 expression helps maintain the normal microbiota but is also involved in dysbiosis, infections, autoimmune disease and oral carcinomas, and it has been proposed as a marker of inflammation severity and treatment outcome.^[3]

Because LL-37 is a 37-residue peptide prone to oligomerization and proteolysis, researchers typically verify identity and purity with HPLC and mass spectrometry certificates of analysis.

Regulatory and Research Status

LL-37 is not approved by the US Food and Drug Administration for any use, and it remains an investigational research peptide. It has been assigned the international nonproprietary name ropocamptide.

The literature retrieved for this page consists largely of reviews, in-vitro studies, animal models and analyses of naturally occurring LL-37 in human tissue. None of the indexed abstracts reports a controlled clinical trial of exogenous LL-37.

Reviewers list several hurdles before clinical use: proteolytic instability, possible toxicity at high concentrations, and the need for better delivery methods and combinations with existing antibiotics.^[6] Proposed future directions include stable synthetic analogs and use of LL-37 levels as a biomarker, for example in periodontitis and sepsis.^[1][8] In dermatology, reviewers have suggested antimicrobial peptides such as LL-37 as an additional approach within barrier repair strategies for atopic dermatitis, a skin disease in which patients are prone to cutaneous infections.^[9]