We have previously shown that 3BP2 is negatively regulated by tankyrase through ADP-ribosylation followed by RNF146-mediated polyubiquitylation and proteasomal destruction (15), while missense mutations in the SH3BP2 gene stabilize 3BP2 proteins, which results in a genetic inflammatory disorder, cherubism (19, 39). Here, RNF146 is linked to cherubism.