Mutation of genes in the autophagy pathway, including immunity-related GTPase M (IRGM) (Parkes et al., 2007; McCarroll et al., 2008), leucine rich repeat serine/threonine-protein kinase 2 (lrrk2) (Barrett et al., 2008; Gardet et al., 2010), Ulk1 (Henckaerts et al., 2011), Atg16l1 (Hampe et al., 2007), and Nod2 (Hugot et al., 2001; Ogura et al., 2001), predisposes individuals to severe CD. Here, IRGM is linked to Cowden disease.