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The accumulation of misfolded proteins in the ER lumen results in ER stress.

The N-terminal domain of IRE1 protein senses the ER stress and gets activated to initiate the unfolded protein response or UPR.

The activated IRE1 molecules form homodimers and use their cytosolic kinase domains to phosphorylate each other.

The dimerized IRE1 molecules club together in a rod-shaped complex forming a surface with endoribonuclease activity.

This surface splices out an intron from the pre-mRNA encoding a transcription factor, X-box binding protein one or XBP1.

The mature mRNA translates into XBP1 protein, which is imported into the nucleus.

Inside the nucleus, XBP1 binds ER response elements on the DNA, activating the transcription of UPR target genes, like chaperones.

Next, the chaperone encoding mRNAs are exported out of the nucleus and bound by ribosomes.

The ribosomes carry the mRNAs to the ER membrane for cotranslational translocation.

As a result, there is an increased influx of chaperone molecules in the ER lumen.

These chaperones correctly refold misfolded proteins so that they can be cleared from the ER.