Phospholipid phosphatase-related protein type 4 (PLPPR4)

Phospholipid phosphatase-related protein type 4 (PLPPR4) is a neuron-specific, postsynaptic density membrane protein highly expressed in the brain, particularly in dendritic compartments of neurons[1][2][3]. It is a member of a family related to lipid phosphate phosphatases but contains structural changes that render it catalytically inactive as an enzyme[1]. Instead, PLPPR4 modulates cell signaling through direct binding, internalization, and modulation of lysophosphatidic acid (LPA), affecting synaptic plasticity, dendritic spine density, and axonal outgrowth[2][3][4]. Functionally, PLPPR4 is implicated in the regulation of glutamatergic synaptic transmission, integrin-mediated cell adhesion, and neuronal morphology[1]. Haploinsufficiency or loss-of-function mutations of PLPPR4 are associated with neurodevelopmental disorders, such as intellectual disability and autism spectrum disorder, likely by impairing the mTOR signaling pathway and neuronal plasticity[3]. Recent evidence also implicates PLPPR4 in cancer metastasis and suggests possible connections with psychiatric and cognitive symptoms. No direct pharmacological modulators of PLPPR4 are clinically approved, though the downstream pathway can be influenced by drugs like fingolimod that activate PP2A[1].

Other names

Phospholipid phosphatase related 4PLPPR4KIAA0455LPPR4PRG1PRG-1PHP1Brain-specific phosphatidic acid phosphatase-like protein 1Inactive 2-lysophosphatidate phosphatase PLPPR4Lipid phosphate phosphatase-related protein type 4Plasticity-related gene 1 proteinPlasticity related gene-1LPR4

Not a direct drug target; fingolimod activates PP2A, which interacts downstream of PLPPR4[1]. General modulation of lysophosphatidic acid (LPA) internalization and signaling.