Peripheral nerve injury results in axonal degeneration and in phenotypic changes of the surrounding Schwann cells, whose presence is critical for nerve regeneration. Using differential screening strategies, we identified a novel protein, termed ninjurin (for nerve injury-induced protein), that is up-regulated after axotomy in neurons and in Schwann cells surrounding the distal nerve segment. Ninjurin is located on the cell surface, is capable of mediating homophilic adhesion, and promotes neurite extension of dorsal root ganglion neurons in vitro. Ninjurin is also expressed in a number of other tissues, predominantly in epithelial cells. These results suggest that ninjurin plays a role in nerve regeneration and in the formation and function of other tissues.