IRE1 (Inositol-Requiring Enzyme 1) is one of three resident transmembrane endoplasmic reticulum (ER) proteins that sense and signal distress from improper protein synthesis and conformation. (While IRE1 alpha is almost universally expressed and IRE1 beta is confined to the gut, both will be conflated as IRE1 here.)  Secreted and transmembrane proteins are primarily produced in