Kaser et al. reported that mice lacking XBP1 in intestinal endothelial cells (IECs) exhibited inefficient UPR, leading to an increase in ER stress, hyperactivation of IRE1, and increased JNK phosphorylation, thus further inducing inflammatory responses in IECs and resulting in the development of spontaneous inflammatory bowel disease (IBD) [29, 30]. This evidence concerns the gene ERN1 and inflammatory bowel disease.