PERK, a type 1 endoplasmic reticulum (ER) membrane kinase, mediates eIF2 alpha phosphorylation at Ser51 during the UPR (unfolded protein response). Protein synthesis is inhibited, thereby reducing the burden of protein substrate for the ER folding and degradation mechanism. Phosphorylation of eIF2 alpha by PERK also selectively promotes the expression of UPR target genes such as Chop and BiP. PERK may also play a role in tumor cell adaptation to hypoxic stress by regulating the translation of angiogenic factors necessary the development of functional microvessels. Mutations in PERK are responsible for the rare autosomal-recessive disorder, Wolcott-Rallison syndrome (WRS).