Recently, IRE1α-mediated X-box–binding protein-1 (XBP1) signaling was reported to promote GVHD (9, 17), but the mechanism of how the ER stress sensors PERK and XBP1 regulate T cell allogeneic response and GVHD induction is essentially uncharacterized. This evidence concerns the gene ERN1 and graft versus host disease.