ERN1 and neoplasm: UPR activation may activate autophagy to remove misfolded proteins accumulated in the ER lumen, inducing conversion of LC3 I to LC3 II and the formation of autophagosomes, leading to protective autophagy and alleviating ERS.[33,34] ERS also activates autophagy by negatively regulating the Akt serine/threonine kinase (Akt)/TSC/mechanistic target of rapamycin kinase pathway and positively regulating the IRE1α-JNK pathway.[35] However, excessive ERS induces autophagy in tumor cells, which eventually leads to cell death.