The conjugation of ubiquitin to proteins is an important means to regulate protein activity for many cellular processes. Targeting of proteins by ubiquitination occurs in three main steps that involve the activation of ubiquitin by E1 enzymes, the carrying of ubiquitin to the target protein by E2 enzymes and the ligation of ubiquitin to the target protein by E3 enzymes. Ring finger protein 40 (RNF40) is a member of the RING type E3 ubiquitin ligases. RNF40 forms a complex with RNF20 to carry out H2B monoubiquitination in association with hPAF and the UbcH6 ubiquitin E2-conjugating enzyme. H2B monoubiquitination by RN40/RNF20 has been shown to be associated with increased H3 methylation and gene transcription.