MGST3 encodes a microsomal glutathione S-transferase with dual enzymatic functions in cellular detoxification and eicosanoid metabolism. The protein catalyzes conjugate addition of reduced glutathione to unsaturated eicosanoids such as leukotriene A4 and 15-deoxy-Δ12,14-prostaglandin J2, forming glutathione adducts that modulate inflammatory responses, and catalyzes glutathione-dependent reduction of eicosanoid peroxides to hydroxides. Recent evidence indicates MGST3 plays broader roles beyond lipid mediator synthesis. In triple-negative breast cancer, mutant p53 protects tumors from ferroptosis through NRF2-dependent upregulation of MGST3, which detoxifies lipid peroxides as a glutathione-dependent peroxidase 1. In rheumatoid arthritis, the small-molecule inhibitor geranyl hydroquinone targets MGST3 in neutrophils to suppress reactive oxygen species production, N1 polarization, and pain hypersensitivity, demonstrating superior analgesic efficacy compared to methotrexate 2. In Alzheimer disease, MGST3 regulates BACE1 protein translation through an RGS4-mediated AKT signaling pathway independent of its canonical eicosanoid metabolism, thereby controlling amyloidogenesis 3. MGST3 expression is heterogeneous across breast tumors, particularly in regions associated with detoxification, suggesting potential implications for chemotherapy resistance 4.