IRGM and Cowden disease: Genes involved in resolving ER stress, for example, UPR-related XBP1 (26) and AGR2 (27), autophagy-related ATG16L1 (28), IRGM1 (29), and LRRK2 (30) are known susceptibility genes for CD, and deletions or mutations in these genes lead to Paneth cell abnormalities.