CHOP is another primary target of induction of cell death after stress activation of ER.[27] It can be activated transcriptionally through all three branches of UPR: IRE1α, PERK/ATF4, and ATF6.[36] Treatment of pancreatic cancer cells with IRE1α inhibitors still caused induction of CHOP, suggesting CHOP was activated through ATF4 and ATF6. Here, EIF2AK3 is linked to familial pancreatic carcinoma.