IRE1α Recombinant Rabbit mAb (S-3873-25)

IRE1α (Inositol-requiring enzyme 1 alpha) is a highly conserved transmembrane serine/threonine kinase and endoribonuclease located in the endoplasmic reticulum (ER) membrane, serving as the most ancient and evolutionarily preserved sensor of the Unfolded Protein Response (UPR) that activates when misfolded proteins accumulate within the ER lumen. Under stress conditions, IRE1α oligomerizes and autophosphorylates to trigger its RNase domain, which specifically splices a 26-nucleotide intron from the mRNA encoding XBP1 (X-box binding protein 1) in mammals; this unconventional splicing event causes a frameshift that produces the potent transcription factor XBP1s, which subsequently migrates to the nucleus to upregulate genes involved in ER chaperone production, lipid biosynthesis, and ER-associated degradation (ERAD) to restore proteostasis. However, if ER stress is prolonged or severe, hyperactivated IRE1α can switch to a pro-apoptotic mode by degrading other mRNAs through Regulated IRE1-Dependent Decay (RIDD) or recruiting apoptosis signal-regulating kinase 1 (ASK1) to initiate cell death pathways, thereby acting as a critical decision-maker that determines whether a cell adapts to stress or undergoes programmed elimination, with its dysregulation being implicated in various pathologies including diabetes, neurodegenerative diseases, and cancer.