The accumulation of misfolded proteins in the ER is cytotoxic, prompting cancer cells to activate UPR pathways mediated by inositol-requiring enzyme 1a (IRE1a), activating transcription factor 6 (ATF6), and protein kinase RNA-like endoplasmic reticulum kinase (PERK) to mitigate ER stress (19). This evidence concerns the gene ERN1 and cancer.