GPX2 (glutathione peroxidase 2) is a cytosolic selenium-dependent enzyme that catalyzes the reduction of hydroperoxides including H2O2, cumene hydroperoxide, and fatty acid-derived hydroperoxides in a glutathione-dependent manner, thereby regulating cellular redox homeostasis 12. GPX2 is predominantly expressed in gastrointestinal epithelium where it contributes to at least 50% of total GPX activity 3. Beyond antioxidant functions, GPX2 plays complex physiological roles in mucosal homeostasis through Wnt pathway signaling and maintains H2O2 homeostasis in signaling cascades 45. GPX2 expression is regulated by Nrf2 activators and upregulated in response to metabolites like indole-3-lactic acid, enhancing protection against intestinal inflammation 6. However, GPX2 exhibits a "Janus-faced" role in cancer pathogenesis: it is markedly overexpressed in hepatocellular carcinoma tissues and correlates with poor survival and lenvatinib resistance, where suppression of GPX2 increases ROS levels and induces apoptosis 7. Similarly, in drug-tolerant cancer persisters, GPX2 suppression triggers lethal ROS accumulation 8. GPX2 is also implicated in atherosclerosis pathogenesis through microbe-metabolite-host interactions 9. These findings suggest GPX2 represents a promising therapeutic target across multiple malignancies.