The IRE1 arm of the UPR is the most evolutionarily conserved of all three pathways . Two isoforms of IRE1 are present in mammals: the globally expressed IRE1⍺; and IRE1β, which is only expressed in goblet cells of the lung and the intestinal epithelium . IRE1 has dual activity as a kinase and as an endoribonuclease . Once activated, IRE1 splices X-box binding protein 1 (XBP1) mRNA, producing a 26 nt spliced transcript (XBP1s), a potent transcription factor for genes containing either the ER stress response element (ERSE) or UPR element (UPRE) . IRE1 also directly degrades ER targeted mRNA, thereby reducing the protein translational load of the ER in a process termed regulated IRE1-dependent decay (RIDD) . IRE1 is further associated with nuclear factor-kappa β (NF-ϰβ) and Jun NH2-terminal kinase (JNK)-mediated signalling, and hence the signalling pathways of cytokine release and apoptosis .