Despite the well-described actions of NRF2 on cell survival processes, including the attenuation of oxidative stress, enhancement of NRF2 signaling by deletion of its repressor, Keap1 failed to impede, and in fact exacerbated, the extent and duration of cholestasis evoked by Rbpjκ depletion from hepatoblast lineage cells. The gene discussed is RBPJ; the disease is cholestasis.