Granulysin

experimental

Also known as: Lymphokine LAG-2, Protein NKG5, T-cell activation protein 519, GNLY, P22749

Granulysin, also known as Lymphokine LAG-2 or Protein NKG5, is a cationic antimicrobial protein expressed primarily by cytotoxic T lymphocytes and natural killer cells. Its mechanism of action involves direct membrane disruption of target cells, including bacteria, fungi, and parasites, through electrostatic interactions with negatively charged microbial membranes. This leads to pore formation, osmotic lysis, and pathogen death. Additionally, granulysin can induce apoptosis in intracellular pathogens by activating caspase-dependent pathways and has been shown to synergize with perforin and granzymes to enhance cytotoxic activity against infected cells. Key research findings demonstrate that granulysin exhibits broad-spectrum antimicrobial activity against *Mycobacterium tuberculosis*, *Plasmodium falciparum*, and various Gram-positive and Gram-negative bacteria. Studies have also identified its role in modulating immune responses, including chemotaxis and activation of dendritic cells. Reduced granulysin expression has been correlated with increased susceptibility to infections, particularly in immunocompromised individuals, while elevated levels are observed in certain autoimmune conditions, suggesting a dual role in host defense and inflammation. Clinically, granulysin is being investigated as a potential biomarker for infectious disease severity and as a therapeutic agent for drug-resistant infections. Experimental models have explored its use in combination with conventional antibiotics to enhance efficacy against multidrug-resistant pathogens. However, its clinical application remains limited due to challenges in delivery, stability, and potential off-target effects on host cells. Further research is needed to validate its safety and efficacy in human trials. For research purposes only — not medical advice.

Key data

Category
Immune Modulation
Sequence
MATWALLLLAAMLLGNPGLVFSRLSPEYYDLARAHLRDEEKSCPCLAQEGPQGDLLTKTQELGRDYRTCLTIVQKLKKMVDKPTQRSVSNAATRVCRTGRSRWRDVCRNFMRRYQSRVTQGLVAGETAQQICEDLRLCIPSTGPL
Molecular weight
16374 g/mol
Research status
experimental
References
639
Tags
uniprot, 3d-structure, alternative-splicing, antibiotic, antimicrobial, disulfide-bond, fungicide, proteomics-identification, reference-proteome, secreted, signal

Mechanism of action

Antimicrobial protein that kills intracellular pathogens. Active against a broad range of microbes, including Gram-positive and Gram-negative bacteria, fungi, and parasites. Kills Mycobacterium tuberculosis

Research & studies

GNLY+CD8+ T cells bridge premature aging and persistent inflammation in people living with HIV
Emerging microbes & infections · 2025 · PubMed
Tissue origin and virus specificity shape human CD8(+) T cell cytotoxicity
Science immunology · 2025 · PubMed
Immune landscape of isocitrate dehydrogenase-stratified primary and recurrent human gliomas
Neuro-oncology · 2024 · PubMed

22 distinct immune cell types were identified in gliomas.; Recurrent gliomas show reduced microglia and increased CD8+ T cells independent of IDH status.; IDH-wild-type gliomas exhibit antigen-presenting microglia and cytotoxic CD8+ T cells.; Novel inflammatory microglia subpopulations expressing granulysin were discovered.

Multiomic single-cell sequencing defines tissue-specific responses in Stevens-Johnson syndrome and toxic epidermal necrolysis
Nature communications · 2024 · PubMed
Single-cell transcriptome analysis and protein profiling reveal broad immune system activation in IgG4-related disease
JCI insight · 2023 · PubMed
Characterizing the tumor microenvironment of metastatic ovarian cancer by single-cell transcriptomics
Cell reports · 2021 · PubMed

9 major cell types identified, including cancer, stromal, and immune cells; Patient samples stratified into high T cell infiltration (high T inf) and low T cell infiltration (low T inf) groups; High T inf group enriched with TOX-expressing CD8+ Trm and granulysin-expressing CD4+ T cell clusters; Unique plasmablast, plasma B cell, and NR1H2+IRF8+ and CD274+ macrophage clusters found in high T inf group

Single-cell landscape of immunological responses in patients with COVID-19
Nature immunology · 2020 · PubMed
Granulysin: The attractive side of a natural born killer
Immunology letters · 2020 · PubMed

Frequently asked questions

What is Granulysin?

Granulysin, also known as Lymphokine LAG-2 or Protein NKG5, is a cationic antimicrobial protein expressed primarily by cytotoxic T lymphocytes and natural killer cells. Its mechanism of action involves direct membrane disruption of target cells, including bacteria, fungi, and parasites, through electrostatic interactio

How does Granulysin work?

Antimicrobial protein that kills intracellular pathogens. Active against a broad range of microbes, including Gram-positive and Gram-negative bacteria, fungi, and parasites. Kills Mycobacterium tuberculosis

What is the research status of Granulysin?

Granulysin is currently classified as experimental, with 639 research references on record. This is for research purposes only and is not medical advice.

What is the molecular weight of Granulysin?

Granulysin has a molecular weight of approximately 16374 g/mol.

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