PLPP1PLPP3

Phosphatidic acid phosphatases PLPP1 and PLPP3 (also known as lipid phosphate phosphatases 1 and 3) are membrane‐associated enzymes that catalyze the dephosphorylation of bioactive phospholipid mediators such as phosphatidic acid, sphingosine‑1‑phosphate and lysophosphatidic acid. Both proteins are members of the type 2 lipid phosphate phosphatase (LPP) family and share a conserved six‑transmembrane domain architecture. PLPP1 is encoded by the PLPP1 gene on chromosome 10 and is expressed predominantly in the central nervous system, skeletal muscle, and skin, where it contributes to myelin maintenance, muscle repair, and epidermal barrier formation. PLPP3 is encoded by the PLPP3 gene on chromosome 7 and shows a broader expression pattern, being abundant in vascular endothelium, kidney, and intestine.

The catalytic activity of PLPP1 and PLPP3 regulates cellular concentrations of inorganic phospholipids, thereby influencing signaling pathways involved in proliferation, migration, and apoptosis. Dysregulation of PLPP1 has been linked to neurodegenerative disorders, psoriasis, and susceptibility to bacterial infections, whereas altered PLPP3 expression is associated with cardiovascular disease, inflammatory bowel disease, and certain cancers. Although PLPP1 and PLPP3 share functional similarities, they exhibit distinct tissue localization and substrate preferences, underscoring their complementary roles in lipid signaling and homeostasis.