We cloned a novel protocadherin cDNA, which we named OL-protocadherin (OL-pc), from mouse brain cDNA libraries. Its cytoplasmic region showed no similarities to other protocadherins, indicating that it belongs to a novel subfamily of protocadherins. Experiments using transfectants showed that OL-pc is a homophilic cell-cell adhesion molecule. The molecular mass of OL-pc was 140 kDa in the brain. Expression of OL-pc mRNA was specific to the nervous system, changing over time from the embryonic stage to the adult stage. The OL-pc expression seemed to be restricted to a subset of functionally related brain nuclei and regions such as the nuclei in the main olfactory system, the limbic system, and the olivocortical projection. There were at least two distinct patterns of distribution for the OL-pc protein. First, it was localized in particular brain nuclei or compartments, such as the stripes of the developing cerebellum. Second, it was found at the synapse in regions such as the glomeruli of the olfactory bulb. In addition, the OL-pc protein seemed not to be detected or was detected only weakly in some regions, such as hippocampus in which the mRNA was expressed at high levels. These results indicate that the expression of OL-pc is developmentally regulated in a subset of the functional systems and that it may be involved in the formation of the neural network by segregation of the brain nuclei and mediation of the axonal connections.