Lysophosphatidic acid (LPA) is a bioactive lipid molecule with a phosphate, a glycerol, and a fatty acid in its structure. The cellular effects of LPA include proliferation, migration, cytokine secretion, and morphological change. These pleiotropic actions allow LPA to participate in a wide variety of biological processes, such as brain development, oncogenesis, wound healing and cancer progression¹. To date, at least 6 subtypes of LPA receptor have been identified. The LPA1–3 receptors are members of the endothelial cell differentiation gene (Edg) family. LPA4, a member of the purinergic receptor family, and the recently identified LPA5 are structurally distant from the canonical Edg LPA1–3 receptors. LPA4 and LPA5 are linked to G_q, G_12/13 and G_s but not G_i, while LPA1–3 all couple to G_i in addition to G_q and G_12/13².

LPA4 (P2Y9/GPR23) was cloned as an orphan GPCR and is closely related to the purinergic P2Y receptors³. Like all GPCRs it has seven transmembrane helices (TMHs) connected by three extracellular loops (ECLs), and three intracellular loops (ICLs); the N-terminus is on the extracellular side of the membrane, and the C-terminus is on the cytoplasmic side⁴.

LPA4 is weakly expressed; there are high levels only in ovary².

LPA4-deficient mice display abnormalities in the blood vascular systems, which caused lethality of embryos and neonates⁵.