NOD2 and Cowden disease: Given that loss-of-function mutations in NOD2 or ATG16L1 are associated with the development of CD (Cho, 2008; Chen et al., 2009; Philpott et al., 2014; Caruso et al., 2020), it is plausible that signaling pathways mediated by intact NOD2 and ATG16L1 prevent chronic inflammation of the gastrointestinal tract.