Neurons regulate the expression of genes essential to individual neuron function through elegant combinatorial interactions among a limited number of transcription factors. In addition, an economy of regulatory control is practiced within the nucleus that belies conceptual divisions of transcription factors into "repressors" and "activators." Studies of the neural restrictive silencer element (NRSE, also known as RE1) and its repressor protein have revealed a multitude of mechanisms by which transcriptional regulation is not only elaborated in normal neuronal development, but perverted in disease states.