GZMA (granzyme A) is a serine protease abundant in cytotoxic T lymphocytes and natural killer cells that mediates target cell death through caspase-independent pyroptosis 1. The protein functions as a key effector molecule delivered via the immunological synapse, cleaving after basic residues (lysine or arginine) to activate pyroptotic pathways 1. GZMA's primary mechanism involves cleaving gasdermin B (GSDMB), releasing its pore-forming N-terminal domain to trigger pyroptotic cell death 12. The enzyme also cleaves APEX1 and the nucleosome assembly protein SET, disrupting DNA repair and enabling nuclear DNA degradation 1. Beyond canonical cytotoxic functions, GZMA exhibits tissue-protective roles: in inflammatory bowel disease, CD8+CD39+ T cells promote intestinal epithelial barrier function through GZMA-mediated suppression of ferroptosis, enhancing tight junction protein expression 3. In pathological contexts, GZMA expression characterizes inflammatory T cell subsets in severe asthma 4 and neoantigen-reactive CD8+ T cells in gastrointestinal cancers 5. GZMA+ T cells also identify transdifferentiated regulatory T cells (exTreg cells) that acquire cytotoxic functions in atherosclerosis 6. Clinically, GZMA expression patterns correlate with immune response intensity and therapeutic outcomes in cancer immunotherapy 7, suggesting its utility as a biomarker for immune competence and potential target for immunomodulation.