ATG5 is a critical component of the autophagy machinery that plays essential roles in cellular homeostasis, inflammation regulation, and disease pathogenesis. The protein functions as part of the ATG12-ATG5-ATG16 complex to facilitate autophagosome formation and maturation 1. ATG5 promotes ferroptosis by degrading ferritin through autophagy, releasing iron that contributes to lipid peroxidation and cell death 2. In inflammatory contexts, ATG5 exhibits complex regulatory functions: it can suppress NLRP3 inflammasome activation when stabilized by deubiquitinating enzymes 1, but also mediates pyroptosis when regulated by TRIM45 in septic encephalopathy 3. ATG5 is crucial for specialized autophagy processes including lipophagy, where it degrades lipid droplets and can induce ferroptosis in corneal epithelial cells 4, and mitophagy, where it helps maintain mitochondrial quality control in diabetic kidney disease 5. Clinically, ATG5 dysfunction is implicated in multiple pathological conditions including depression through hyperactive neuronal autophagy that depletes BDNF 6, organ fibrosis via endothelial autophagy deficiency 7, and cancer where it mediates drug-induced autophagic cell death 8. These findings highlight ATG5 as a potential therapeutic target for various diseases involving autophagy dysregulation.