Contrary to our expectation, the symptoms of cholestasis evoked by depleting NOTCH signaling were enhanced by NRF2 signaling in the livers of Keap1F/F::RbpjF/F::AlbCre mice and were extended through the growth stage until at least 9 W. Consequently, remarkable hepatomegaly and hypercholesterolemia accompanied by hepatic damage were amplified and sustained (Figure 1 and Figure 2). This evidence concerns the gene NFE2L2 and familial hypercholesterolemia.