Overall our findings, besides confirming the impairment of NRF2 in FRDA and evidencing a role for the “Keap-1/DJ1/p62” axis in mediating its deficiency, highlight the susceptibility of the transcription factor to the drugs’ induction, and provide suggestions for a “multi-target” drugs’ effect of the NRF2-mediated protection. The gene discussed is PARK7; the disease is Friedreich ataxia.