Dysregulation of ISR signaling, particularly eIF2α phosphorylation, has been linked to many neurological disorders that are characterized by neuroinflammation, disturbances in protein homeostasis and oxidative stress including multiple sclerosis (MS), Alzheimer's disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), Huntington disease, vanishing white matter disorder, frontotemporal dementia, neurotrauma, and prion disorders [19, 45]. The gene discussed is EIF2A; the disease is Alzheimer disease.