Granulysin (GNLY)

Granulysin is a cytolytic and proinflammatory protein produced by human cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells (PMID: 14499265). It belongs to the saposin-like protein (SAPLIP) family and exists in two main isoforms: a constitutively secreted 15-kDa precursor and a 9-kDa active form stored in cytolytic granules (PMID: 11178344). The 9-kDa form exhibits broad-spectrum antimicrobial activity against bacteria (including Mycobacterium tuberculosis), fungi, and parasites, as well as tumoricidal activity (PMID: 10644038). It functions by permeabilizing target membranes and inducing apoptosis or 'microptosis' through mitochondrial and metabolic disruption (PMID: 31103451). Clinically, granulysin serves as a critical biomarker for severe cutaneous adverse reactions like Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), where its overproduction leads to massive keratinocyte death (PMID: 19029993). It is also being explored as a therapeutic agent, with recombinant forms and immunotoxins under development for treating drug-resistant infections and various cancers (PMID: 32859066). Its ability to selectively target microbial membranes over cholesterol-rich mammalian membranes provides a potential therapeutic window for novel antibiotic development.

Other names

LAG-2T-cell activation protein 519NKG5TLA519Lymphokine LAG-2

Granulysin acts by disrupting the lipid membranes of target cells or microbes, leading to pore formation and increased permeability (PMID: 14499265). In microbes, it induces 'microptosis' by disrupting oxidative metabolism and energy generation (PMID: 31103451). In mammalian cells, it triggers apoptosis through mitochondrial damage, the release of cytochrome C, and the activation of caspases (PMID: 10644038). Therapeutic strategies involve using recombinant granulysin to kill pathogens or tumors, or using antibodies to neutralize its activity in inflammatory conditions (PMID: 32859066).