Our study added another cytoprotective mechanism to the repertoire of NRF2 functions by demonstrating its profound influence on energy metabolism, thus supporting the usefulness of NRF2 activation in a wide range of pathological conditions and inspiring the Reata Pharmaceuticals-led clinical development of the NRF2 activator omaveloxolone (SkyclarysTM) for Friedreich's ataxia patients. Here, NFE2L2 is linked to Friedreich ataxia.