In addition to HRI, mammalian cells possess three other eIF2α kinases, which are expressed in different tissues and activated by specific physiological stresses, namely GCN2, activated by nutrient deprivation; PKR, which responds to viral infection; and PERK, activated by endoplasmic reticulum (ER) stress28,46–50. Here, EIF2AK4 is linked to viral infectious disease.