In support of this hypothesis, treatment of FDXRR386W/R386W cells with omaveloxolone resulted in translocation of NRF2 to the nucleus, increasing expression of NRF2 target genes such as SLC7A11. Similarly, FdxrR389W/R398W mice showed increased expression of NRF2 and SLC7A11 following omaveloxolone treatment, as well as a corresponding improvement in survival and other morbidities such as paraphimosis (Fig. 6). Here, NFE2L2 is linked to paraphimosis.