Members of the semaphorin protein family are involved in axonal guidance during neural development. Semaphorin 5a is thought to have a bifunctional role in axon guidance, exerting both attractive and inhibitory effects on developing axons associated with limbic function. The thrombospondin repeats of Semaphorin 5a physically interact with both heparan sulfate proteoglycans and chondroitin sulfate proteoglycans, inducing attractive and inhibitory guidance cues, respectively. The biological responses to Semaphorin 5a are induced through binding to its high-affinity receptor, plexin B3, triggering intracellular signaling through Met.