Semaphorin 3E (Sema3E) is a secreted protein that functions in axon guidance and/or vascular tip cell guidance during development. Sema3E signals through Plexin D1 that may also be associated with Neuropilin 1 and/or VEGF R2. It can exert axon repulsive or attraction effects, promote axonal growth, the development of glutamatertic synaptic development, and the development of GnRH producing neurons. Sema3E also plays a role in the regulation of vascular growth and branching. It inhibits smooth muscle cell proliferation and migration in the asthmatic airway, promotes hepatic stellate cell activation and wound healing, and regulates the migration of developing thymocytes. Sema3E is upregulated by inflammatory macrophages and damaged hepatocytes. It can be cleaved to generate a form that does not dimerize and is highly expressed in tumor cell lines with metastatic potential.