Activation of the ISR with its characteristic increase in eIF2 phosphorylation has been reported in numerous neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Frontotemporal Dementia, Amyotrophic Lateral Sclerosis, and prion neurodegenerative diseases, but its role in disease progression has just recently begun to be interrogated (Kim et al., 2013; Leitman et al., 2014; Ma et al., 2013; Moreno et al., 2013, 2012). Here, EIF2S3 is linked to Alzheimer disease.