Among the molecular mechanisms responsible for mitochondrial dysfunction in DS, we found that the dosage-related over-expression of a corepressor mapping to the chromosome 21 (Hsa21), namely NRIP1, inhibits the activity of the transcriptional activator PGC-1α (Izzo et al., 2014), a gene that orchestrates mitochondrial biogenesis and function (Scarpulla et al., 2012). This evidence concerns the gene PPARGC1A and Dravet syndrome.