The ISR arm of the UPR is centered on the phosphorylation of the α-subunit (eIF2α) of heterotrimer eIF2, which is catalysed by PERK [42] or three other kinases (general control nonderepressible 2 (GCN2), PKR and heme-regulated inhibitor (HRI)), that are activated by distinct stresses (amino acid deprivation, viral infection and heme deficiency, respectively) [43,44,45]. Here, EIF2AK4 is linked to viral infectious disease.