Collapsin response mediator proteins (CRMPs), including CRMP-1 (DRP-1), CRMP-2 (DRP-2 or TOAD64), CRMP-3 (DRP-4), CRMP-4 (DRP-3) and CRMP-5 (DRP-5), mediate signal transduction after exposure of neural cells to the axon guidance molecule Semaphorin 3A (SEMA3A)/collapsin. CRMPs are present in the developing cerebral cortex and neocortical neurons and are responsive to SEMA3A. In the adult brain, the expression of CRMPs is dramatically downregulated. However, they remain expressed in structures that retain their capacity for differentiation and plasticity. CRMP-3 is expressed transiently in developing spinal cord and selectively in the postnatal cerebellum. It is cleaved by Calpain to produce a p54 N-terminal fragment. This cleavage product translocates to the nucleus and induces neuronal death in response to excitotoxicity and cerebral ischemia.