This notion is solidly based on the gene-targeting experimental evidence revealing those unique pathophysiological phenotypes of Nrf1 but not Nrf2, as evinced in those distinct tissue-specific knockout mice (see section "Unique pathophysiological phenotypes of Nrf1 that are distinctive from Nrf2"), as well by their specific knockout cell lines from the human hepatoma (Figure 13A). This evidence concerns the gene NRF1 and hepatocellular carcinoma.