Autophagy is generally activated by conditions of nutrient deprivation but has also been associated with a number of physiological processes including development, differentiation, neurodegeneration, infection, and cancer. Mammalian Atg16L1, containing an amino-terminal coiled coil domain and carboxyl-terminal WD-repeats, has multiple isoforms produced by alternative splicing. Atg16L1 provides a functional link between the two crucial ubiquitin-like conjugation systems of autophagy. Atg16L1 binds Atg5 of the Atg12-Atg5 conjugate forming an 800 kDa multimeric complex. Hypomorphic Atg16L1 mice also show defects in autophagy and abnormalities in intestinal Paneth cell function similar to that found in Crohn's disease.