SET and MYND-containing domain 3 (SMYD3), a protein methyltransferase with multiple histone and non-histone targets, is overexpressed in human HCC, and deletion of Smyd3 prevents DEN-induced liver tumor development in mice (Sarris et al., 2016; Zhang et al., 2021). Here, SMYD3 is linked to hepatocellular carcinoma.