ATG16L1 (autophagy-related 16 like 1) is a core autophagy protein essential for autophagosome biogenesis that functions as a molecular hub coordinating both canonical and non-canonical autophagy pathways 1. In canonical autophagy, ATG16L1 interacts with the ATG12-ATG5 conjugate to form an E3-like complex that catalyzes lipidation of ATG8 family proteins (including LC3) with phosphatidylethanolamine, enabling autophagosomal membrane elongation 2. ATG16L1 membrane recruitment is regulated through multiple mechanisms, including S-palmitoylation by ZDHHC7, which enhances formation of ATG16L1 complexes with WIPI2B and RAB33B on the phagophore 2. In non-canonical autophagy, ATG16L1 mediates conjugation of ATG8 proteins to single endolysosomal membranes, a process critical for LC3-associated phagocytosis and immune responses to intracellular pathogens 3. The V-ATPase recruits ATG16L1 to damaged compartments via direct binding of the V1H subunit, coupling organellar acidification defects to ATG8 targeting during infection or immune stimulation 4. ATG16L1 plays protective roles in metabolic dysfunction-associated steatohepatitis by promoting macrophage lipophagy 5, and variants are associated with inflammatory bowel disease. Loss of ATG16L1 increases susceptibility to infection and metabolic dysfunction, while its enhancement promotes cellular homeostasis and immune defense.