LPAR1

Lysophosphatidic acid receptor 1 (LPAR1) is a G protein-coupled receptor that mediates lysophosphatidic acid (LPA) signaling to regulate cellular proliferation, migration, and differentiation^[1][2]. Mechanistically, LPAR1 activates downstream pathways including PI3K/AKT, AKT/mTOR/HIF-1α, and Rho/ROCK-SRF, which coordinate metabolic remodeling, cytoskeletal organization, and transcriptional activity^[3][4][5][6]. In disease models, LPAR1 promotes keratinocyte proliferation in psoriasis, modulates intratumoral heterogeneity in ovarian serous cystadenocarcinoma, and influences fibrosis in kidney and lung tissues^[3][2][7]. Compared with related isoforms such as LPAR3 and LPAR6, LPAR1 exhibits preferential expression in enteric glia, keratinocytes, and specific cancer cells, providing a distinct functional role in motility, skin homeostasis, and tumor progression^[6][7][8]. Pharmacologically, selective antagonists such as Ki16425, VPC12249, and GS-2278 inhibit LPAR1 signaling, attenuating glycolysis, cell proliferation, fibrosis, and enhancing radiosensitivity in cancer models^[3][2][9]. Agonists or inhibitors targeting LPAR1 enable experimental modulation of signaling axes for preclinical studies, offering translational potential for treating inflammatory, fibrotic, and neoplastic diseases^{[2][3][9][10]}. LPAR1 also interacts with Filamin A and MRTF-A to regulate cytoskeletal dynamics and transcriptional programs, underscoring its integrative role in both normal physiology and pathological contexts^[1].