One known difference is that newly synthesized Nrf1 is anchored to the endoplasmic reticulum, undergoes Vcp/p97-dependent turnover by the proteasome, and is sensitive to insufficient proteasome activity [14,29,30,31], whereas newly synthesized Nrf2 is localized to the cytosol, forms a heterodimeric complex with kelch-like ECH-associated protein 1, is sensitive to ROS, and can be regulated by the ubiquitin-binding adaptor molecule p62, also known as Sqstm1, which has a major role in HCC development [13,32,33,34,35]. This evidence concerns the gene NRF1 and hepatocellular carcinoma.