CNS white matter is selectively inhibitory for axonal outgrowth. Nogo is an oligodendrocyte-specific member of the reticulon family and is a component of CNS white matter that prevents axonal regeneration in the adult CNS. Nogo is expressed by oligodendrocytes and associates primarily with the endoplasmic reticulum. The extracellular domain of Nogo, designated Nogo-66 inhibits axonal extension, but does not alter non-neuronal cell morphology. Expression of a brain-specific, leucine-rich-repeat protein with high affinity for Nogo-66, the Nogo-66 receptor (Nogo-R), is sufficient to impart Nogo-66 axonal inhibition to unresponsive neurons. Disruption of the interaction between Nogo-66 and Nogo-R potentially provides for enhanced recovery after human CNS injury. Nogo-R is widely expressed in the brain, with the highest levels of expression in the gray matter of the CNS. In addition, low levels of Nogo-R mRNA are expressed in heart and kidney.