PRDX6 is a multifunctional thiol-specific peroxidase that catalyzes reduction of hydrogen peroxide and organic hydroperoxides to water and alcohols, respectively, providing cellular protection against oxidative stress 1. Beyond its canonical peroxidase activity, PRDX6 exhibits phospholipase A2 (iPLA2) activity and acyl-CoA-dependent lysophospholipid acyltransferase activity, enabling both reduction and remodeling of phospholipids 12. Mechanistically, PRDX6 acts as a selenium-acceptor protein facilitating intracellular selenium utilization and selenoprotein incorporation, including ferroptosis-protective glutathione peroxidase 4 (GPX4) 3. This selenium-delivery function occurs through interaction with selenophosphate synthetase 2 (SEPHS2), representing an alternative selenocysteine metabolism pathway 4. Genetically, PRDX6-AS1 variants associate with systemic lupus erythematosus susceptibility, with elevated PRDX6 expression in patient immune cells 5. Functionally, PRDX6-iPLA2 activity regulates neuroinflammation post-ischemic stroke via ROS generation and astrocyte-microglia crosstalk 6, while PRDX6 inhibition by apigenin suppresses senescence-associated secretory phenotype development 7. In cancer, PRDX6 mediates ferroptosis resistance through NRF2-dependent mechanisms 8 and mitophagy inhibition in non-alcoholic steatohepatitis 9.