ATG3 is an E2-like conjugating enzyme that catalyzes a critical step in autophagosome formation by conjugating ATG8-family proteins (including LC3 and GABARAP) to phosphatidylethanolamine lipids in membranes, generating the lipidated forms required for autophagosomal isolation membranes. ATG3 cycles between the E1 enzyme ATG7 and the E3 complex (ATG12–ATG5–ATG16L1) to deliver activated ATG8-family proteins to membranes, and also acts as a membrane curvature sensor that enhances lipidation by detecting lipid-packing defects. Beyond canonical autophagy, ATG3 participates in the ATG12–ATG3 conjugate, which regulates late endosome-to-lysosome trafficking and basal autophagosome maturation via interaction with PDCD6IP, and promotes primary ciliogenesis through autophagic removal of OFD1. In disease contexts, ATG3 expression is elevated in non-alcoholic fatty liver disease (NAFLD); inhibition of ATG3 ameliorates hepatic steatosis independently of its autophagic role, instead by enhancing mitochondrial function through the SIRT1–CPT1a axis 1. ATG3 also contributes to ferroptotic cell death in cancer cells 2, and higher ATG3 expression in B-cell lymphoma tumors correlates with resistance to CAR-T cell immunotherapy 3. These findings position ATG3 as both a central autophagy regulator and a node for metabolic and immunological control with potential therapeutic implications.