ATG7 is an E1-like activating enzyme essential for autophagy, functioning as a critical hub in cellular homeostasis and stress responses. Mechanistically, ATG7 activates ubiquitin-like proteins ATG12 and ATG8 family members for their conjugation with ATG5 and phosphatidylethanolamine, respectively, enabling autophagosome formation and LC3-II lipidation 1. ATG7 regulates diverse cellular processes including mitophagy for mitochondrial quality control, ferroptosis through ferritin degradation 2, and HMGB1 release during ferroptotic cell death 3. In immune contexts, ATG7 restricts intracellular Mycobacterium tuberculosis replication in human macrophages 4. ATG7 influences post-ischemic angiogenesis through HIF1A regulation via a non-canonical autophagy-independent pathway involving STAT1 suppression 5. Beyond canonical autophagy, ATG7 functions in endothelial cell protection during hyperglycemia 6 and orchestrates vascular smooth muscle cell senescence through an ATF3-ATG7 feedback loop 7. During sepsis, ATG7-dependent autophagy ameliorates liver injury by restraining proinflammatory macrophage activation through HIF-1α degradation 8. Importantly, ATG7 expression is suppressed in osteoarthritis fibroblast-like synoviocytes through METTL3-mediated m6A modification, promoting senescence 9. These multifaceted roles underscore ATG7's importance in preventing age-related and metabolic diseases.