The Nrf2 transcription factor has long been identified as a modulator of autophagy [[111], [112], [113], [114]], and is also associated with the Unfolded Protein Response (UPR) [100,[115], [116], [117], [118], [119], [120]], which might explain its ability to reduce pathologic protein aggregation in several proteinopathies, including prion diseases [121,122]. This evidence concerns the gene NFE2L2 and proteostasis deficiencies.