Lysophosphatidic acid receptor 4 (LPA4) (LPA4)

Lysophosphatidic acid receptor 4 (LPA4), also known as LPAR4 or GPR23, is a member of the G protein-coupled receptor (GPCR) family that specifically binds the bioactive phospholipid lysophosphatidic acid (LPA) [1, 2]. Distinct from the Edg-family LPA receptors (LPA1-3), LPA4 is phylogenetically related to the P2Y purinergic receptor family [2, 3]. It is uniquely characterized by its ability to couple with multiple G-protein subtypes, including Gs, Gq, Gi, and G12/13, which allows it to trigger a wide array of intracellular signaling cascades such as cAMP production and Rho-mediated cytoskeletal changes [3, 4]. Biologically, LPA4 is essential for proper vascular development and bone homeostasis, and it significantly influences cell motility and shape [1, 5]. In clinical contexts, aberrant LPA4 signaling is associated with cancer progression, particularly in its role in modulating the tumor microenvironment and promoting metastasis [4]. Although therapeutic targeting of LPA4 is still in the early stages compared to other LPA receptors, selective small-molecule antagonists like ONO-9480389 are being investigated for potential applications in treating cancer and fibrotic disorders [2, 4]. The receptor's involvement in diverse physiological processes makes it a complex but promising target for precision medicine [1, 3].

Other names

LPAR4P2Y9P2RY9G-protein coupled receptor 23GPR23

Modulation of intracellular signaling pathways via G12/13, Gq, Gs, and Gi proteins to influence cytoskeletal rearrangement and gene expression.