Ubiquitination is an important mechanism through which three classes of enzymes act in concert to target short-lived or abnormal proteins for destruction. The three classes of enzymes involved in ubiquitination are the ubiquitin-activating enzymes (E1s), the ubiquitin-conjugating enzymes (E2s) and the ubiquitin-protein ligases (E3s). RNF40 (RING finger protein 40), also known as BRE1B, Staring or RBP95, is a 1,001 amino acid nuclear protein that contains one RING-type zinc finger. Expressed ubiquitously with highest expression in heart, testis and pancreas, RNF40 functions as an E3 ubiquitin-protein ligase that regulates the monoubiquitination and subsequent degradation of select residues on target proteins, such as Histone H2B and Syntaxin 1. In addition, RNF40 forms a ubiquitin ligase complex with UBCH6 (an E2 enzyme) and together, these proteins play a crucial role in regulation of the histone code. Four isoforms of RNF40 exist due to alternative splicing events.