Like other E3 ligases, TRIM21 functions by ubiquitination of target substrates.[25] A high expression of TRIM21 arrests the HCC cells cycle and inhibits cells proliferation by promoting ATG4B ubiquitylation,[26] and suppresses the invasion of HCC cells by promoting β-catenin ubiquitylation and degradation.[27] TRIM21 negatively regulates the NF-κB which is known as lymphoma proliferation and survival factor by the ubiquitylation and translocation of IKKβ to autophagosomes.[28,29] Therefore, it might be the mechanism of TRIM21. This evidence concerns the gene TRIM21 and hepatocellular carcinoma.