Upon ER stress, GRP78/BiP can trigger autophagy to improve the survival of cancer cells through three different UPR pathways including eukaryotic translation initiation factor 2 alpha kinase 3/PKR-like ER kinase (EIF2AK3/PERK), endoplasmic reticulum to nucleus signaling 1/inositol-requiring enzyme 1 (ERN1/IRE1), and activating transcription factor 6 (ATF6), which target the ATG16L1 complex, MAPK/JNK and X-box binding protein 1 (XBP1), and the AKT-mTOR pathway, respectively [349,350,351,352]. The gene discussed is HSPA5; the disease is cancer.