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We identified and cloned the cDNA encoding a Nova-interacting protein that we termed br-PTB (for brain-enriched polypyrimidine tract binding protein. Polydorides AD, Okano HJ, Yang YYL, Stefani G, and Darnell RB. Proc Natl Acad Sci, USA, 97, 6350-6355, 2000.) Functional studies have demonstrated that brPTB is able to bind pre-mRNA and antagonize Nova's action as an intronic splice enhancer. Further biochemical and CLIP analysis of brPTB function in neurons awaits a genetic system.