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:12665549, PubMed:18849966, PubMed:23392225, PubMed:24553140, PubMed:24954904, PubMed:33586810). Acts as a molecular hub, coordinating autophagy pathways via distinct domains that support either canonical or non-canonical signaling (PubMed:33586810). 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 (By similarity). Thereby, controls the elongation of the nascent autophagosomal membrane (By similarity). 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 (By similarity). Non-canonical autophagy plays a key role in epithelial cells to limit lethal infection by influenza A (IAV) virus (PubMed:33586810). Regulates mitochondrial antiviral signaling (MAVS)-dependent type I interferon (IFN-I) production (By similarity). Negatively regulates NOD1- and NOD2-driven inflammatory cytokine response.Instead, promotes with NOD2 an autophagy-dependent antibacterial pathway (PubMed:24238340). Plays a role in regulating morphology and function of Paneth cell (By similarity). Homodimer (By similarity). Homooligomer (PubMed:12665549). Heterooligomer with ATG16L2 (PubMed:22082872). Interacts with WIPI1 (By similarity). Interacts with WIPI2 (PubMed:24954904). Interacts with RB1CC1; the interaction is required for ULK1 complex-dependent autophagy (PubMed:23392225, PubMed:23262492). Interacts with ATG5 (PubMed:12665549). 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). Interacts with RAB33B (PubMed:18448665). Interacts (via WD repeats) with TMEM59; the interaction mediates unconventional autophagic activity of TMEM59 (By similarity). Interacts with TLR2 and NOD2 (By similarity). Interacts (via WD repeats) with MEFV (By similarity). Interacts (via N-terminal) with CLTC (By similarity). Interacts with NOD2 (By similarity). Interacts with TUFM (By similarity). Interacts with TRIM16 (By similarity). Interacts (via WD repeats) with SPATA33 (PubMed:33087875). Recruited to omegasomes membranes by WIPI2 (PubMed:24954904). Omegasomes are endoplasmic reticulum connected strutures at the origin of preautophagosomal structures. Localized to preautophagosomal structure (PAS) where it is involved in the membrane targeting of ATG5 (PubMed:24954904). Localizes also to discrete punctae along the ciliary axoneme (PubMed:24954904). Upon activation of non-canonical autophagy, recruited to single-membrane endolysosomal compartments (By similarity). Widely expressed (PubMed:12665549). Expressed in the testis and sperm midpiece (at protein level) (PubMed:33087875). Expressed in liver. Highly expressed in liver. Expressed in brain. 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. Belongs to the WD repeat ATG16 family. Extended N-terminus.