Phospholipid phosphatase-related protein type 3 (PLPPR3)

Phospholipid phosphatase-related protein type 3 (PLPPR3) is a member of the PLPPR family, which evolved from canonical phospholipid phosphatases but lacks essential catalytic residues, rendering it an inactive hydrolase. PLPPR3 is membrane-associated, bears a long intracellular C-terminal domain with unique conserved motifs (including a polyglutamate region), and is especially abundant in developing axons. It directly interacts with PTEN, modulating its localization and activity, thereby influencing PI(3,4,5)P3-dependent signaling pathways crucial for axonal filopodia development and neuronal complexity. Unlike canonical lipid phosphatases, PLPPR3 is thought to function as an atypical lysophosphatidic acid (LPA) receptor/sensor, controlling neuronal responses to LPA and associated morphological changes. Variants and dysfunctions have been associated with pseudopseudohypoparathyroidism and acrodysostosis. Key points: - PLPPR3 is structurally related to but functionally distinct from active phospholipid phosphatases, lacking catalytic activity due to amino acid substitutions. - It is not a classic GPCR or LPA receptor but shares some downstream signaling features. - Roles in neuronal morphogenesis and potential for involvement in disease link it to the broader context of cell migration, neural development, and possibly pathologies related to cell shape changes. No approved drugs directly target PLPPR3 as of current literature, and its clinical utility as a biomarker or drug target remains largely investigative.

Other names

LPPR3PRG2PRG-2FLJ11535PAP-2-like protein 2Plasticity-related gene 2 proteinLPR3inactive phospholipid phosphatase PLPPR3lipid phosphate phosphatase-related protein type 3

No direct drugs or inhibitors described; mechanistic actions include modulation of PI3K/PTEN signaling and interactions affecting filopodia/branching in neurons