The unfolded protein response (UPR) is a eukaryotic cell process that addresses ER stress. UPR is initiated by three ER-localized sensors: PKR-like ER kinase (PERK), activating transcription factor 6 (ATF6), and inositol-requiring enzyme 1 alpha (IRE1 alpha). UPR-downstream signaling is modulated by the ATF6 and IRE1-XBP1 pathways.