The innate UPR sensor PERK is a member of the protein kinase family associated with the protein translation initiation complex. Activated PERK specifically phosphorylates the eukaryotic translation initiation factor 2⍺ (eIF2⍺), which reduces the load on the ER by attenuating the translation of select mRNA . This decrease to the ER protein translational load serves as the most immediate response to ER stress, as it is not reliant upon nuclear translocation of transcription factors, transcription, or translation . Paradoxically, phosphorylated eIF2⍺ promotes the translation of select mRNAs such as the activated transcription factor 4 (ATF4). PERK also directly phosphorylates nuclear factor erythroid 2-related factor 2 (NRF2), allowing its nuclear translocation where it functions as an additional transcription factor in conjunction with ATF4 .