C-terminal binding proteins (CtBPs) can be found in vertebrates (e.g., rat and human) and arthropods (e.g., Drosophila melanogaster), yet members studied enzymatically include only two human paralogs. The animal CtBPs localize to both nucleus and cytoplasm. CtBPs were first identified as transcriptional co-repressors targeting many transcriptional regulators and playing critical roles during development of both invertebrates and vertebrates. Although the precise mechanism of the co-repressor activity is still under investigation, it is known that CtBPs recognize the consensus PXDLS motif in DNA-binding and other transcription-related proteins. They also possess a dehydrogenase activity, and the NAD-dependent conformational change is thought to be essential to their co-repression activity.