EIF2AK1 and hyperinsulinemic hypoglycemia, familial, 4: eIF2 plays an important role in sensing metabolic status and cellular stress and, consequently, its activity is highly regulated by four known protein kinases that respond to distinct stress stimuli—protein kinase R (PKR) is activated by double-stranded RNA (dsRNA), PKR-like ER kinase (PERK) senses unfolded proteins in the ER, and GCN2 and heme-regulated inhibitor (HRI) are activated by nutrient starvation and heme deficiency, respectively [85].