The Nogo receptor is a brain-specific protein that is most highly expressed in the gray matter of the CNS. Nogo-R binds with high affinity to the extracellular domain of Nogo, a component of CNS white matter that prevents axonal regeneration in the adult CNS. Binding of Nogo-R to Nogo is sufficient to elicit Nogo axonal inhibition to unresponsive neurons. Disruption of the interaction between Nogo and its receptor may provide for enhanced recovery after human CNS injury.