ATG16L1

ATG16L1, or Autophagy Related 16 Like 1, is a protein encoded by the ATG16L1 gene in humans. It is a core component of the autophagy machinery and is essential for the early steps of autophagosome formation. ATG16L1 forms a large complex with ATG5 and ATG12, which localizes to the expanding phagophore and functions as an E3-like factor that facilitates LC3 lipidation and autophagosome maturation.

Its N-terminal region binds ATG5, and a central coiled-coil domain mediates dimerization, enabling the assembly of the ATG5-ATG12-ATG16L1 complex. A C-terminal region participates in complex function. In mammalian cells, ATG16L1 localizes to pre-autophagosomal structures in the cytosol and is recruited to the phagophore during autophagy.

Beyond canonical autophagy, ATG16L1 contributes to selective autophagy (xenophagy) and host defense against intracellular pathogens; it also influences inflammatory signaling and immune responses, particularly in intestinal tissues.

A common T300A missense variant of ATG16L1 is associated with increased risk of Crohn's disease, likely by impairing autophagic clearance of bacteria and modulating intestinal inflammation.

ATG16L1 is conserved among eukaryotes; in humans it has multiple isoforms produced by alternative splicing. The gene belongs to the autophagy-related gene family, with functional interactions with other core autophagy enzymes such as ATG5, ATG12, and ATG7.