EIF2AK3 and amyotrophic lateral sclerosis: Activation of the PERK signaling cascade initially results in the repression of protein synthesis, but eventually triggers apoptosis if proteostasis is not achieved.10,11 Activation of inositol-requiring enzyme 1 and activating transcription factor 6 pathways promotes the upregulation of UPR-responsive genes.10 Of the three UPR pathways, there is growing evidence that PERK-UPR response is involved in a number of neurodegenerative conditions that share pathological similarities with TBI, including Alzheimer's disease, amyotrophic lateral sclerosis, and frontotemporal dementia.11