Ephrin type-B receptor 4(EPHB4) is also known as HTK, MYK1 and TYRO11,is a member of Eph family. The Eph family of receptors are divided into 2 groups based on the similarity of their extracellular domain sequences and their affinities for binding ephrin-A and ephrin-B ligands. Ephrin receptors make up the largest subgroup of the receptor tyrosine kinase (RTK) family. The protein encoded by EPHB4 binds to Ephrin-B2 and plays an essential role in vascular development. EPHB4 and its ligand ephrin-B2 are specifically expressed on venous and arterial endothelial cells, respectively, and play an essential role in vascular development via bidirectional signals. The forward EPHB4 signaling inhibits cell adhesion, chemotaxis, angiogenesis and tumor growth. Incontrast, the reverse Ephrin-B2 signaling exerts the opposite effect. It has been reported that aberrant expression of EPHB4 is associated with prostate cancer and highly malignant breast cancers, accordingly, EPHB4 has potential application as a therapeutic candidate.