The Eph receptors are the largest family of receptor tyrosine kinases. They can be grouped into two subclasses based on sequence homology: the EphA and the EphB receptors. The ligands for the Eph receptors are the ephrins. The EphA receptors bind ephrin-A ligands, which are tethered to the membrane by a GPI linkage, and the EphB receptors bind ephrin-B ligands, which have a membrane spanning region. The Eph receptors are widely expressed during embryonic development, including in the nervous system and the vascular system. Ephrins and Eph receptors have been implicated in many developmental processes including neuronal network formation, guidance of cell migration, and axonal pathfinding. They remain expressed at lower levels in adult tissues and are upregulated in pathological conditions such as cancer. EphB4 is expressed in epithelial cells and in endothelial cells of embryonic veins, where its signaling mediates cell migration and proliferation via the PI3K pathway. It is upregulate