When eIF2α is phosphorylated, the global protein synthesis process is attenuated.112 The unfolded protein response sensor PERK is activated by high levels of misfolded proteins to phosphorylate and globally inhibit the translation factor eIF2α.113 Dysregulated levels of eIF2α and other cellular stress biomarkers have been observed in specimens from ALS patients and disease models.114 Modulation of eIF2α phosphorylation or upstream factors has emerged as a potential therapeutic approach. This evidence concerns the gene EIF2A and amyotrophic lateral sclerosis.