Plays an essential role in both canonical and non-canonical autophagy: interacts with ATG12-ATG5 to mediate the lipidation to ATG8 family proteins (MAP1LC3A, MAP1LC3B, MAP1LC3C, GABARAPL1, GABARAPL2 and GABARAP) (PubMed:23376921, PubMed:23392225, PubMed:29317426, PubMed:30778222, PubMed:33909989, PubMed:24553140, PubMed:24954904, PubMed:27273576). Acts as a molecular hub, coordinating autophagy pathways via distinct domains that support either canonical or non-canonical signaling (PubMed:29317426, PubMed:30778222). During canonical autophagy, interacts with ATG12-ATG5 to mediate the conjugation of phosphatidylethanolamine (PE) to ATG8 proteins, to produce a membrane-bound activated form of ATG8 (PubMed:23376921, PubMed:23392225, PubMed:24553140, PubMed:24954904, PubMed:27273576). Thereby, controls the elongation of the nascent autophagosomal membrane (PubMed:23376921, PubMed:23392225, PubMed:24553140, PubMed:24954904, PubMed:27273576). Also involved in non-canonical autophagy, a parallel pathway involving conjugation of ATG8 proteins to single membranes at endolysosomal compartments, probably by catalyzing conjugation of phosphatidylserine (PS) to ATG8 (PubMed:33909989). Non-canonical autophagy plays a key role in epithelial cells to limit lethal infection by influenza A (IAV) virus (By similarity). Regulates mitochondrial antiviral signaling (MAVS)-dependent type I interferon (IFN-I) production (PubMed:22749352, PubMed:25645662). Negatively regulates NOD1- and NOD2-driven inflammatory cytokine response (PubMed:24238340). Instead, promotes with NOD2 an autophagy-dependent antibacterial pathway (PubMed:20637199). Plays a role in regulating morphology and function of Paneth cell (PubMed:18849966). Homodimer (PubMed:25484072). Homooligomer (By similarity). Heterooligomer with ATG16L2 (By similarity). Interacts with WIPI1 (PubMed:28561066). Interacts with WIPI2 (PubMed:24954904, PubMed:28561066). Interacts with RB1CC1; the interaction is required for ULK1 complex-dependent autophagy (PubMed:23262492, PubMed:24954904, PubMed:23392225). Interacts with ATG5 (PubMed:23202584, PubMed:24191030, PubMed:25484072, PubMed:26812546). Part of either the minor and major complexes respectively composed of 4 sets of ATG12-ATG5 and ATG16L1 (400 kDa) or 8 sets of ATG12-ATG5 and ATG16L1 (800 kDa) (PubMed:26083323, PubMed:29317426, PubMed:30778222, PubMed:23202584, PubMed:24191030). Interacts with RAB33B (PubMed:21808068). Interacts (via WD repeats) with TMEM59; the interaction mediates unconventional autophagic activity of TMEM59 (PubMed:23376921, PubMed:27273576). Interacts with TLR2 and NOD2 (PubMed:23376921). Interacts (via WD repeats) with MEFV (PubMed:26347139). Interacts with PPP1CA; the interaction dephosphorylates ATG16L1 causing dissociation of ATG12-ATG5-ATG16L1 complex (PubMed:26083323). Interacts (via N-terminal) with CLTC (PubMed:20639872). Interacts with NOD2 (PubMed:20637199). Interacts with TUFM (PubMed:22749352). Interacts with TRIM16 (PubMed:30143514). Interacts (via WD repeats) with SPATA33 (PubMed:33087875). Recruited to omegasomes membranes by WIPI2 (By similarity). Omegasomes are endoplasmic reticulum connected strutures at the origin of preautophagosomal structures (By similarity). Localized to preautophagosomal structure (PAS) where it is involved in the membrane targeting of ATG5 (By similarity). Localizes also to discrete punctae along the ciliary axoneme (By similarity). Upon activation of non-canonical autophagy, recruited to single-membrane endolysosomal compartments (PubMed:29317426). The WD repeats are required for non-canonical autophagy but not for canonical autophagy. Proteolytic cleavage by activated CASP3 leads to degradation and may regulate autophagy upon cellular stress and apoptotic stimuli. Phosphorylation at Ser-139 promotes association with the ATG12-ATG5 conjugate to form the ATG12-ATG5-ATG16L1 complex. Disease susceptibility is associated with variants affecting the gene represented in this entry. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. Belongs to the WD repeat ATG16 family. Wrong choice of CDS. Truncated N-terminus.