AbstractC-terminal binding proteins (CtBPs) were initially identified as binding partners for the E1A-transforming proteins. Although the invertebrate genome encodes one CtBP protein, two CtBPs (CtBP1 and CtBP2) are encoded by the vertebrate genome and perform both unique and duplicative functions. CtBP1 and CtBP2 are closely related and act as transcriptional corepressors when activated by nicotinamide adenine dinucleotide binding to their dehydrogenase domains. CtBPs exert transcriptional repression primarily