BEND6 (BEN domain containing 6) is a nuclear transcription corepressor with dual roles in neural development and innate immunity. In neural stem cells, BEND6 functions as a corepressor of the CSL transcription factor CBF1, antagonizing Notch signaling to suppress neural stem cell self-renewal and promote neurogenesis 1. BEND6 binds CBF1 and inhibits Notch-dependent target gene activation; its recruitment to Notch-regulated enhancers is promoted by CBF1 but antagonized by activated Notch 1. Loss of BEND6 increases neural stem cell self-renewal, while ectopic expression promotes neurogenesis in both in utero and cultured neurosphere systems 1. Beyond neural development, BEND6 functions as a negative regulator of innate immune responses 2. It is an interferon-stimulated gene upregulated by RNA virus-induced interferon-β 2. BEND6 inhibits the antiviral interferon response by targeting IRF3: it prevents IRF3 recruitment by TBK1, blocks IRF3 phosphorylation and dimerization, and directly binds ISRE sequences to inhibit IRF3 DNA binding and IFN-β transcription 2. These activities promote replication of various RNA viruses 2, identifying BEND6 as a potential therapeutic target for viral infections.