Endocrine gland-derived vascular endothelial growth factor (EG-VEGF), also called prokineticin 1 (PK1), is a member of the prokineticin family of secreted proteins that share a common structural motif containing ten conserved cysteine residues that form five pairs of disulfide bonds. Members of this family include the mammalian EG-VEGF/ PK1 and PK2, as well as the venom protein A (VPRA) from the venom of black mamba snake and the frog Bombina variegata, Bv8. Human EG-VEGF precursor is a 105 amino acid (aa) residue protein with a 19 aa signal peptide that is cleaved to yield a 86 aa mature protein. EG-VEGF is expressed in multiple tissues including the gastrointestinal (GI) tract and steroidogenic glands (testis, ovary, placenta and adrenal glands). EG-VEGF has been shown to potently stimulate the contraction of GI smooth muscle. In addition, EG-VEGF is a tissue-specific angiogenic factor that exhibits biological activities similar to that of VEGF on select cells. It induces the proliferation, migration, and fenestration in cultured endocrine gland-derived capillary endothelial cells. EG-VEGF binds to and activates two closely related G proteincoupled receptors, EG-VEGF/ PK1R1 and EG-VEGF/ PK2R2. Activation of the receptors leads to stimulation of phosphoinositide turnover and activation of p44/p42 MAP kinase signaling pathways.