GZMH (granzyme H) is a cytotoxic serine protease primarily expressed in immune effector cells that plays critical roles in cell-mediated immunity and cytotoxic responses. The protein functions as part of cytotoxic T lymphocyte signatures, with GZMH expression serving as a marker for cytotoxic CD8+ T cells in systemic lupus erythematosus 1 and being included in cytolytic T-lymphocyte transcriptomic signatures alongside other granzymes (GZMA, GZMB, GZMM) and perforin (PRF1) 2. GZMH demonstrates significant upregulation in various pathological contexts, including post-transplant renal fibrosis where it serves as a hub biomarker 3 and in different stroke clot types where it indicates cytotoxic activity 4. The gene shows enhanced expression in terminally differentiated cytotoxic CD4+ T cells in radiation-induced brain injury, suggesting involvement in tissue damage mechanisms 5. Notably, hydroxychloroquine treatment significantly upregulates GZMH expression in effector CD8+ T cells, contributing to improved cytotoxicity 6. GZMH expression correlates with immune system activation and appears in various disease contexts including glioblastoma progression 7, indicating its broad significance in immune-mediated pathological processes and potential as a biomarker for cytotoxic immune responses.