Receptor tyrosine Kinase VEGFR-3, also known as FLT4, together with VEGFR1 (FIT1) and VEGFR2 (KDR/Flk-1), are the receptors for vascular endothelial growth factors (VEGF). The VEGFR family belongs to the class II subfamily of receptor tyrosine kinases (RTKs), containing a large extracellular region which is composed of seven Ig-like domains (D1–D7), a single transmembrane, helix, and a cytoplasmic region with tyrosine kinase activity. In VEGFR-3, the fifth Ig homology domain is proteolytically cleaved which results in polypeptides that remain linked by two disulfide bonds. VEGFR-3 is widely expressed on all endothelial cells in early embryogenesis, while, in adult tissues, VEGFR-3 expression disappears from the vascular endothelial cells and is observed only on the lymphatic endothelium. VEGF-C and VEGF-D activation of VEGFR-3 plays an important role in the formation of the lymphatic vessel system. Aberrant activation or expression of VEGFR and their ligands has been implicated in tumor angiogenesis, coronary artery disease, diabetic blindness, and other diseases.