SERPINB9 (serpin family B member 9) functions as an endogenous inhibitor of granzyme B, a cytotoxic protease released by cytotoxic T lymphocytes and natural killer cells 1. The protein serves as a protective mechanism against potentially harmful effects of granzyme B within immune system cells 1. However, SERPINB9 plays a complex role in cancer and immune responses. In tumor contexts, SERPINB9 expression contributes to immune evasion by protecting cancer cells from granzyme B-mediated cytotoxicity 23. Genetic ablation of SERPINB9 results in tumor cell death through granzyme B-dependent mechanisms and enhances protective T cell-based immunity 3. The protein is expressed in HIV-1-infected cytotoxic CD4+ T cells that resist cell death, contributing to viral persistence 4. Additionally, SERPINB9 directly interacts with spermine synthase, preventing its degradation and promoting spermine accumulation in the tumor microenvironment, which creates immunosuppressive conditions by inducing CD8+ T cell dysfunction 5. SERPINB9 expression is induced by oncogenic pathways and represents a mechanism of immunosuppression in various cancers including prostate and pancreatic cancers 65. Targeting SERPINB9 shows therapeutic promise for enhancing immunotherapy responses 35.