Under conditions of ER stress, misfolded proteins accumulate in the ER lumen. IRE1 senses this accumulation and undergoes oligomerization and autophosphorylation, activating its endoribonuclease domain. This leads to the unconventional splicing of X-box binding protein 1 (XBP1) mRNA, resulting in the production of a potent transcription factor that upregulates genes involved in protein folding, secretion, and degradation. Additionally, IRE1 can degrade other mRNAs in a process known as regulated IRE1-dependent decay (RIDD), which helps alleviate protein load in the ER.
