Vascular endothelial growth factor D (VEGF-D) is a homodimeric ligand of VEGF R3/Flt-4 and is synthesized with N- and C-terminal propeptides. Fully processed VEGF-D containing only the VEGF homology domain can additionally bind and activate VEGF R2/KDR/Flk-1. VEGF-D is expressed in adult lung, heart, muscle, and small intestine, and is most abundantly expressed in fetal lungs and skin. VEGF R3 is strongly expressed in lymphatic endothelial cells and is essential for regulation of the growth and differentiation of lymphatic endothelium. While VEGF-C is the critical ligand for VEGF R3 during embryonic lymphatic development, while VEGF-D is most active in neonatal lymphatic maturation and bone growth.