EIF2AK3 and supranuclear palsy, progressive, 1: However, when the PERK arm of the UPR is activated by thapsigargin, PERK from haplotype B homozygote cells is more active in phosphorylating eIF2α when compared to PERK from cells homozygous for haplotype A. The haplotype that confers high risk for PSP produces the more active form of PERK, suggesting that activation of the UPR is pathogenic in PSP and not a protective response.