For multi-cellular organisms, the sacrifice of irremediably stressed cells through programmed cell death is an ultimate and fail-safe method to ensure protein quality control, and thus to maintain health. Yet over-zealous cell death may cause organ failure and expose organisms to the risk of cell degenerative diseases, such as diabetes mellitus. Many cell degenerative diseases, including diabetes mellitus and some neurodegenerative diseases, are now thought to occur in part from UPR dysregulation. Drug target validation of the IRE1α-TXNIP-IL-1β chain may ultimately lead to therapeutic advances for such diseases.
