Mechanistically, TRIM proteins regulate levels and functions of downstream proteins through ubiquitination-dependent and independent mechanisms, and specific members of TRIM proteins regulate the activity of TGF-β/Smad, MAPK, PI3K-AKT, Wnt/β-catenin, cell cycle, STATs, and RA signaling cascades in HCC (Fig. 5). Here, TGFB1 is linked to hepatocellular carcinoma.