September 26, 2026 · 2 min read

LL-37: the human cathelicidin and its roles in host defense

An overview of LL-37, the only human cathelicidin antimicrobial peptide, covering its antibacterial and immunomodulatory activity in published reviews.

LL-37 is the only cathelicidin humans make. It is a cationic peptide 37 amino acids long, named for the two leucines at its start, and it is cut from a larger precursor protein called hCAP18. Antimicrobial peptides like it work as natural antibiotics in the body's first line of defense. The summary below draws on published reviews.

The LL-37 sequence

Sequence: Leucine, Leucine, Glycine, Aspartic acid, Phenylalanine, Phenylalanine, Arginine, Lysine, Serine, Lysine, Glutamic acid, Lysine, Isoleucine, Glycine, Lysine, Glutamic acid, Phenylalanine, Lysine, Arginine, Isoleucine, Valine, Glutamine, Arginine, Isoleucine, Lysine, Aspartic acid, Phenylalanine, Leucine, Arginine, Asparagine, Leucine, Valine, Proline, Arginine, Threonine, Glutamic acid, Serine.

  • Hydrophobic
  • Glycine or proline
  • Negatively charged
  • Positively charged
  • Polar
Length
37 amino acids
Calculated mass
4,493.3 Da
Net charge
Positive: cationic peptide
The last 37 residues of human cathelicidin antimicrobial peptide (UniProt P49913), released from the precursor protein hCAP18. Named for the two leucines at its start. The mass is calculated from the sequence.

More than an antibiotic

A 2016 review in Pharmacological Reports calls LL-37 a broad-spectrum antibiotic that also has strong chemotactic and immunomodulatory properties. It covers activity in four systems: immune, respiratory, gastrointestinal and skin. The authors tie the pathways that depend on LL-37 to specific diseases and conclude that it deserves further study as a drug candidate.

Roles reported for LL-37

  1. Antimicrobial

    Broad-spectrum activity against microbes.

  2. Chemotactic

    Attracts immune cells.

  3. Immunomodulatory

    Signals to and shapes immune cell responses.

  4. Systems covered

    Immune, respiratory, gastrointestinal and skin.

From Fabisiak et al., Pharmacol Rep 2016, which reviews activity in the immune, respiratory, gastrointestinal and skin systems.

Local infection and inflammation

A 2025 update in Inflammation Research looks at how LL-37 might limit the spread of a local infection through several mechanisms. Other reviews cover its role in heart disease and the link between LL-37 expression and inflammatory responses in severe COVID-19. A 2020 paper studied its therapeutic potential in a murine sepsis model.

A complicated picture

LL-37 both kills microbes and signals to immune cells, so what it does depends on concentration and context. Researchers have reported pro-inflammatory and anti-inflammatory activity, and the balance shifts between tissues and disease states. Read the primary papers carefully and treat broad summaries with some caution.

  • Check whether the work used the full-length peptide or a shortened fragment.
  • Check whether results come from cells, animals or humans.
  • Note the concentration. Activity changes sharply with dose.

LL-37 is highly charged, sticks to labware, and tends to aggregate, so handling and analysis need care. A certificate of analysis should include HPLC purity and a mass spec confirmation of identity.

References

  1. Fabisiak A et al. LL-37: Cathelicidin-related antimicrobial peptide with pleiotropic activity. Pharmacol Rep 2016.
  2. Svensson D et al. Human antimicrobial/host defense peptide LL-37 may prevent the spread of a local infection through multiple mechanisms: an update. Inflamm Res 2025.
  3. Nagaoka I et al. Therapeutic Potential of Cathelicidin Peptide LL-37, an Antimicrobial Agent, in a Murine Sepsis Model. Int J Mol Sci 2020.

Related research notes