EIF2AK3 and hepatocellular carcinoma: Notably, ER stress can activate downstream effectors such as ATF6, IRE1, or PERK to orchestrate the UPR, exerting both physiological and pathological effects.[27] Indeed, only the PERK signaling pathway, and not ATF6 or IRE1 signaling, was detected in hepatoma cells treated with sorafenib (Figure 2C).