IRE1: ER stress sensor and cell fate executor

•IRE1α degrades anti-Casp2 miRNA to initiate cell death.•The phosphor-transfer function of IRE1α is essential for cell fate determination.•IRE1 perceives developmental cues and protein-folding homeostasis distinctly.•Alterations of IRE1α substrate specificity determine cell fates.•There are conserved and unique features between plant and mammalian IRE1.

Cells operate a signaling network termed the unfolded protein response (UPR) to monitor protein-folding capacity in the endoplasmic reticulum (ER). Inositol-requiring enzyme 1 (IRE1) is an ER transmembrane sensor that activates the UPR to maintain the ER and cellular function. Although mammalian IRE1 promotes cell survival, it can initiate apoptosis via decay of antiapoptotic miRNAs. Convergent and divergent IRE1 characteristics between plants and animals underscore its significance in cellular homeostasis. This review provides an updated scenario of the IRE1 signaling model, discusses emerging IRE1 sensing mechanisms, compares IRE1 features among species, and outlines exciting future directions in UPR research.