4μ8C is a potent and selective inhibitor of the endoribonuclease (RNase) domain of IRE1α, a key ER stress sensor in the unfolded protein response (UPR). It specifically blocks IRE1α-mediated splicing of XBP1 mRNA, preventing formation of the active transcription factor XBP1s, without affecting IRE1 kinase activity. This makes it an essential tool for dissecting UPR signaling in research on endoplasmic reticulum (ER) stress responses. Applications include studies of neurodegenerative disorders, cancer, diabetes, fibrosis, and viral infections, where ER stress contributes to pathology. It is used in cell-based assays and preclinical models to explore therapeutic modulation of UPR pathways.