E6AP in the brain: one protein, dual function, multiple diseases.

E6-Associated Protein (E6AP), the founding member of the HECT (Homologus to E6AP C terminus) family of ubiquitin ligases, has been gaining increased attention from the scientific community. In addition to its ubiquitin ligase function, our laboratory has also identified steroid hormone receptor transcriptional coactivation as yet another essential function of this protein. Furthermore, it has been established that E6AP has a role in numerous diseases including cancers and neurological syndromes. In this review, we delineate genetic and biochemical knowledge of E6AP and we focus on its role in the pathobiology of neuro-developmental and neuro-aging diseases; bringing to light important gaps of knowledge related to the involvement of its well-studied ligase function versus the much less studied nuclear receptor transcriptional coactivation function in the pathogenesis of these diseases. Tackling these gaps of knowledge could reveal novel possible neuro-pathobiological mechanisms and present crucial information for the design of effective treatment modalities for devastating CNS diseases.