GZMA

Granzyme A (GZMA), also known as CTLA3 or GrA, is a serine protease secreted by cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. It mediates caspase-independent target cell apoptosis by cleaving the SET complex, releasing active NM23-H1 DNase to fragment DNA. Additionally, GZMA processes pro-inflammatory cytokines like IL-1β, regulating immune responses.
Dysregulated GZMA activity links to autoimmune disorders (e.g., rheumatoid arthritis, lupus) via excessive tissue damage; its deficiency may impair anti-tumor immunity in melanoma or leukemia. Preclinical GZMA inhibitors are tested for autoimmunity, while strategies enhancing its cytotoxicity are explored for cancer immunotherapy—though no FDA-approved drugs exist yet.