In this case, hyperactivation of IRE1α in Atg16l1;Xbp1ΔIEC mice drives CD-like ileitis, whereas IRE1β provides a protective function in this model.19 As inflammation in this specific model likely originates in Paneth cells,26 it may not be related to a role for IRE1β in mucus homeostasis. This evidence concerns the gene ERN2 and Cowden disease.