Several pathways contribute to the failure of protein homeostasis (proteostasis), including those controlling both the initiation58 and elongation59 phases of translation, ribosomal function60-63 and protein degradation.64 Dysregulation of the control of the initiation phase of translation, in particular, via the PERK branch of the UPR, occurs across the spectrum of human neurodegenerative disease.10 In mouse models of neurodegenerative disorders, from Alzheimer’s, Parkinson’s, tauopathies, ALS and prion disease, overactivation of this pathway is associated with pathology and clinical signs. This evidence concerns the gene EIF2AK3 and neurodegenerative disease.