Granzyme B (GZMB) is a serine protease abundantly stored in cytolytic granules of cytotoxic CD8+ T cells and natural killer cells 1. Upon delivery into target cells through the immunological synapse, GZMB executes cytotoxic functions through two primary mechanisms: it catalyzes cleavage of gasdermin-E (GSDME) to trigger pyroptosis 23, and it directly cleaves caspases-3, -7, -9, and -10 to activate apoptosis 4. GZMB expression is tightly regulated; microRNA-27a* negatively regulates GZMB expression to fine-tune NK cell cytotoxicity 5. In cancer immunotherapy, GZMB+ CD8+ T cells infiltrate immunoreactive triple-negative breast cancers and are associated with favorable outcomes 6. Additionally, CD8+ regulatory T cells expressing GZMB suppress autoreactive lymphocytes and prevent autoimmunity 7. Notably, cytotoxic CD4+ T cells expressing GZMB represent an emerging therapeutic target in non-small cell lung cancer, with their effector function restorable through dual PD-1/CD85j blockade and IL-15 stimulation 8. Age-related decline in NKG2C+GZMB- CD8+ T cells occurs during aging 9, while GZMB serves as a prognostic biomarker predicting immunotherapy response in metastatic urothelial carcinoma 10.