Our results show that (a) inhibition of PERK during a period of β cell ER stress in NOD mice reduces insulitis, preserves β cell mass, and delays the development of diabetes; (b) gene expression patterns in β cells following PERK inhibition are consistent with reductions in the UPR and PERK response; and (c) inhibition of PERK activity augments the immune checkpoint protein PD-L1 through stabilization mediated by GOLM1. Here, CD274 is linked to diabetes mellitus.