A disruption in mitochondrial biogenesis, driven by NRF1 dysregulation, has been observed in many neurodegenerative and neurodevelopmental disorders including AD, Parkinson’s disease (PD), and Huntington’s disease (HD), and may play a similar role in widespread neurogenesis or myelination deficits in DS (Satoh et al., 2013; Preciados et al., 2016; Morabito et al., 2021). Here, NRF1 is linked to Parkinson disease.