GSTM5 (glutathione S-transferase mu 5) is a cytosolic enzyme that catalyzes conjugation of reduced glutathione to exogenous and endogenous hydrophobic electrophiles, functioning as a Phase II detoxification enzyme 1. The gene is expressed across multiple tissues including brain, testis, and liver, with a unique 846-nucleotide 3'-noncoding region distinguishing it from other Mu-class glutathione S-transferases 1. GSTM5 serves as a critical antioxidant and genomic stability factor with significant disease relevance. In cancer contexts, GSTM5 functions as a tumor suppressor: low expression in lung adenocarcinoma correlates with shorter overall survival and is driven by promoter hypermethylation 2; similarly, GSTM5 hypermethylation serves as a bladder cancer biomarker 3. In breast cancer, GSTM5 depletion impairs DNA damage repair and confers sensitivity to PLK1 inhibition 4. Environmental pollutants including bisphenol A and TCDD suppress GSTM5 expression, linking exposure to bladder carcinogenesis 5. Beyond cancer, GSTM5 genetic polymorphisms affect chemotherapy response in acute myeloid leukemia 6, and genomic copy number variations correlate with antioxidant defense in age-related macular degeneration 7. In rheumatoid arthritis, the IGF2BP2-GSTM5 axis regulates fibroblast inflammation through mRNA stability control 8. These findings establish GSTM5 as a multi-functional therapeutic target across diverse pathologies.