IRE1 is activated in response to the accumulation of unfolded or misfolded proteins in the ER. Upon activation, IRE1 undergoes dimerization and autophosphorylation, which activates its endoribonuclease domain. This leads to the unconventional splicing of X-box binding protein 1 (XBP1) mRNA, producing a potent transcription factor that upregulates genes involved in protein folding, secretion, and degradation.