EIF2AK3 and cancer: UPR effectors, including ERN1 (IRE1α), ATF6, and PERK (EIF2AK3), dissociate from HSPA5 (GRP78) and activate their respective canonical targets (XBP1s, ATF6α, and ATF4); subsequently trigger transcriptional reprogramming that promotes the survival of cancer cells under ER stress (7).