EIF2AK3 and diabetes mellitus: Initially, in view of the known role of PERK in the UPR, it was proposed that PERK deficiency may result in a defect of the actively secreting β cell to handle the ER stress resulting from this high demand, leading to an accumulation of misfolded proteins, that would become toxic to the cell and lead to apoptosis, resulting in diabetes, independently of an autoimmune process [20,26].