Granzyme A (GZMA)

Granzyme A (GZMA) is a trypsin-like serine protease predominantly expressed in cytotoxic T lymphocytes and natural killer cells, stored in secretory granules and released upon immune activation. Its main function is to induce caspase-independent programmed cell death in target cells by cleaving key DNA repair and nuclear proteins—triggering single-stranded DNA breaks, chromatin condensation, and cell death without caspase activation[1][2][3]. GZMA activates pyroptosis by cleaving gasdermin B and can independently stimulate immune cells (including dendritic cells and monocytes) to secrete proinflammatory cytokines such as IL-1β, TNFα, and IL-6, thereby bridging innate and adaptive immunity[3][4]. Its activities are implicated in immune defense against infections and tumors, as well as in autoimmune and inflammatory pathologies. Currently, no direct clinical inhibitors are in use, but its expression is a valuable biomarker in multiple immunological contexts[4][5].

Other names

Granzyme 1Cytotoxic T-lymphocyte-associated serine esterase 3CTL tryptaseHanukah factorHFSPFragmentin-1Cytotoxic T-lymphocyte proteinase 1H factorCTLA3Hanukkah factorGranzyme-1Hanukkah factor serine protease

For hypothetical inhibitors: Block protease activity; For vaccine/adjuvant use: Enhance immune cell maturation and drive adaptive cytotoxic responses; Modulate inflammatory cytokine production