Protein kinase-like endoplasmic reticulum kinase (PERK) is an eIF2? kinase and transmembrane protein resident in the endoplasmic reticulum (ER) membrane that couples ER stress signals to translation inhibition. ER stress increases the activity of PERK, which then phosphorylates eIF2? to promote reduced translation. Research studies have demonstrated that PERK-deficient mice have defects in pancreatic ? cells several weeks after birth, suggesting a role for PERK-mediated translational control in protecting secretory cells from ER stress. PERK activation during ER stress correlates with autophosphorylation of its cytoplasmic kinase domain. Phosphorylation of PERK at Thr980 serves as a marker for its activation status.