PLPPR4 (phospholipid phosphatase related 4), also known as Plasticity-Related Gene-1 (PRG-1), is a postsynaptic density membrane protein that regulates glutamatergic synaptic transmission through lysophosphatidic acid (LPA)-mediated signaling. PLPPR4 binds LPA and mediates its cellular internalization, modulating neuronal plasticity and axonal outgrowth during development 1. The protein functions by inhibiting LPA-induced effects on cells through its lipid phosphatase activity 2. At the molecular level, PLPPR4 regulates synaptic plasticity via the mTOR signaling pathway 3. Loss-of-function mutations impair dendritic protrusion density, neurite length, and axon development, with disrupted mTOR signaling evidenced by altered p-AKT, p-mTOR, p-ERK1/2, and p-PI3K levels 3. Clinically, PLPPR4 dysfunction associates with neurodevelopmental disorders including intellectual disability and autism spectrum disorder 3. Heterozygous PLPPR4 mutations modify seizure susceptibility in benign familial infantile epilepsy and can aggravate SCN1A-related epilepsy phenotypes 1. Additionally, PLPPR4 expression alterations correlate with prognosis in bladder cancer and gastric cancer, where reduced expression associates with worse outcomes 45. These findings suggest PLPPR4 serves as both a genetic modifier in epilepsy and a prognostic biomarker in malignancies.