There is good genetic evidence that susceptibility to polygenic CD is associated with several common variants affecting autophagy.49 Variants in NOD2 functionally link bacterial recognition to selective antimicrobial autophagy involving ATG16L1.11, 13, 36, 50 Whereas previous studies might have predicted the effect of XIAP deficiency on NOD2-dependent xenophagy, the link to NPC1 represents a novel IBD susceptibility gene. Here, NPC1 is linked to Cowden disease.