A few frequent modifications in NRF2 signaling that have been identified for cancer cells comprise somatic mutations in the KEAP1 or CUL3 genes, epigenetic KEAP1 silencing, accumulation of KEAP1-interacting proteins like p62/SQSTM1, p21, or cysteine modification of an oncometabolite like fumarate [134] (Figure 3). The gene discussed is NFE2L2; the disease is cancer.