One family of inhibitory axon guidance molecules is the semaphorins. The semaphorins include secreted, transmembrane, and GPI-anchored extracellular molecules that have been implicated in neuron development, vascular disease, and tumor progression. There are eight classes of semaphorin genes, all of which are characterized by a conserved 500 amino acid, cystine-rich Sema domain. Semaphorin 3F (Sema-3F) is a class III secreted semaphorin that binds with high affinity to Neuropilin-2, and low affinity to Neuropilin-1. During peripheral and central nervous system development, Sema-3F has critical roles in axon guidance and dendrite outgrowth. Sema-3F has also been shown to inhibit angiogenesis by manipulating VEGFR function and decreasing blood vessel density. In cancers, Sema-3F induces a poorly vascularized, encapsulated, non-metastatic phenotype through chemorepulsion of endothelial cells in melanoma, while Sema-3F disrupts intercellular contacts of MCF7 breast cancer cells through delocalization of E-cadherin and beta-catenin. Thus, Sema-3F may have important roles in axon guidance, angiogenesis, and tumor progression