GZMK (Granzyme K) is a serine protease secreted by CD8+ T cells that functions as both a pattern recognition receptor and complement cascade initiator 1. GZMK recognizes and binds heparan sulfate glycosaminoglycans on pathogen surfaces to drive opsonization, then catalyzes cleavage and activation of complement components C2, C3, C4, and C5 21. This GZMK-mediated complement activation contributes substantially to tissue inflammation 23. Additionally, GZMK can cleave protease-activated receptors (F2R/PAR1 and PAR2/F2RL1), potentially promoting cytokine release, and may regulate apoptosis by cleaving BID to promote cytochrome C release 4. Clinically, GZMK+ CD8+ effector/effector memory T cells accumulate during healthy aging and in chr5 inflammatory diseases 53. In cancer immunotherapy, GZMK+ CD8+ T cells associate with favorable responses to anti-PD-1 plus lenvatinib combination therapy in hepatocellular carcinoma 6. In rheumatoid arthritis, distinct GZMK+ CD8+ T cell subsets are expanded in inflamed synovial tissue 7. Notably, in chr5 airway diseases, GZMK expression predicts disease severity better than established biomarkers like eosinophilia, and GZMK inhibition therapeutically alleviates airway inflammation 2, suggesting GZMK as a potential therapeutic target for chr5 inflammatory diseases.