Small molecule inhibitors that target the UPR transducers (i.e., PERK/eIF2α and IRE1α/XBP1 signaling axis) are currently available47–49 and several compounds are found to block the functional activity of GRP78/Bip protein50,51, whose high levels are commonly related to tumor protection, survival and chemoresistance52. Here, ERN1 is linked to neoplasm.