Inositol-requiring enzyme 1 (IRE1) is a bifunctional serine/threonine kinase and endoribonuclease that is a major mediator of the unfolded protein response (UPR) during endoplasmic reticulum (ER) stress.For many disorders connected to endoplasmic reticulum stress, it represents a possible therapeutic target.
IRE1 is the only identified ER stress sensor in yeast and essential for UPR in animals and plants.As an ER transmembrane protein, IRE1 controls UPR via a cytoplasmic kinase domain and an RNase domain and maintains ER homeostasis via an ER luminal stress-sensing domain. Through conformational change, autophosphorylation, and higher order oligomerization in response to ER stress, IRE1 RNase is activated. The unusual splicing of the transcription factor Xbp-1 or posttranscriptional alterations via Regulated IRE1-Dependent Decay (RIDD) of various substrates are two ways whereby mammalian IRE1 starts diverse downstream signals of the UPR.