These include the transcription factors nuclear factor erythroid-2-related factor 2 (Nrf2), which is critical for redox homeostasis,9 and Forkhead/FOXO transcription factor 3 (FOXO3), which is involved in metabolic homeostasis.10 The second messenger molecule diacylglycerol (DAG) has also been shown to be a PERK substrate.11 As PERK activation is also linked to viral infections, neurodegenerative disorders (e.g., Alzheimer, Parkinson and prion disease)12 and, most notably, to cancer, there has been a growing interest in PERK as a potential clinical option for treatment of these diseases. Here, NFE2L2 is linked to prion disease.