Inflammatory bowel diseases (IBD) are chronic inflammatory disorders affecting the intestinal mucosa. An important hallmark of IBD is increased epithelial cell death causing intestinal barrier disruption that leads to uncontrolled antigen influx and sustained inflammatory responses. Increasing evidence points to a central role for an aberrant unfolded protein response (UPR), which is the adaptive cellular response following stress to the endoplasmic reticulum (ER). Interestingly, the UPR induces cytoprotective pathways, however in case of prolonged stress to the ER, it induces programmed cell death.