The ER can experience stress in a variety of ways, but a central canonical feature of ER stress is the accumulation of misfolded proteins that have overwhelmed the protein-folding capacity of the ER . Genes activated by the UPR largely serve to counteract this ER stress through regulation of protein glycosylation, lipid biogenesis, ER chaperones, ER-associated degradation (ERAD), and protein trafficking to the ER . As a result of UPR activation, increased expression of chaperones and ER expansion increases both the ER folding capacity and volume, while degradation of ER resident proteins and attenuation of protein translation reduces ER load to collectively restore ER homeostasis . However, sustained or prolonged ER stress, indicating that homeostasis cannot be restored, shifts the pro-survival functions of the UPR towards proapoptotic functions .