The four ISR serine-threonine kinases that phosphorylate eIF2α each sense a different stress: PKR-like ER Kinase (PERK) sense endoplasmic reticulum (ER) stress related to protein misfolding and is located within the ER lumen; double-stranded RNA-dependent protein kinase (PKR) responds to viral infection; heme-regulated eIF2α kinase (HRI) which senses heme deficiency; and general control non-derepressible 2 (GCN2) senses amino acid deficiency [3]. The gene discussed is EIF2AK3; the disease is viral infectious disease.