Lysophosphatidic

Lysophosphatidic acid, commonly abbreviated as LPA, is a simple lysophospholipid that acts as a potent extracellular signaling molecule in animals. It consists of a glycerol backbone bearing a single fatty acid chain and a phosphate-containing head group, making it amphipathic and able to participate in membrane-related as well as receptor-mediated signaling.

LPA is generated primarily by the enzyme autotaxin (ENPP2) through hydrolysis of lysophosphatidylcholine, and it can also arise from the deacylation of phosphatidic acid by phospholipases. Its levels are regulated by degradation pathways that include lipid phosphate phosphatases and other lipases, shaping its local and systemic activity.

The biological effects of LPA are mediated mainly through six G protein–coupled receptors, LPA1 through LPA6 (LPAR1–LPAR6). Receptor engagement activates G proteins such as Gi, Gq, and G12/13, triggering signaling cascades including MAPK, PI3K/Akt, and Rho/ROCK pathways. These signals influence cellular processes such as proliferation, survival, migration, cytoskeletal remodeling, and gene expression.

Physiologically, LPA participates in wound healing, angiogenesis, vascular development, and reproductive function. Pathologically, dysregulated LPA signaling has been implicated in cancer progression, fibrosis, neuropathic pain, and inflammatory conditions. Therapeutic strategies targeting autotaxin or LPA receptors are under investigation for fibrosis, cancer, and pain management.

Chemically, LPA species vary by the length and saturation of the fatty acyl chain attached to the glycerol backbone. LPA is present in tissues and circulating fluids at low nanomolar to micromolar levels, reflecting its role as a signaling mediator rather than a storage lipid.