PRRT1 (proline-rich transmembrane protein 1) is a membrane protein that regulates AMPA-type glutamate receptor (AMPAR) trafficking and synaptic transmission. Primary function: PRRT1 maintains an extrasynaptic pool of AMPARs necessary for synapse development and controls basal AMPAR surface expression by regulating phosphorylation levels of GluA1 and GluA2 subunits 1. Mechanism: PRRT1 differentially stabilizes AMPAR GluA1 phosphorylated at distinct residues (S845 and S831) and is required for NMDA receptor-dependent long-term depression and plasticity-induced AMPAR trafficking 1. While dispensable for mature synaptic transmission, PRRT1 plays critical developmental roles in synapse organization and glutamatergic signaling 2. Disease relevance: PRRT1 represents a druggable dispanin family member implicated in neurological disorders 2. Epigenetic alterations at PRRT1 loci show associations with neurodevelopmental disorders including autism spectrum disorder 3, and DNA methylation changes at PRRT1 are significantly associated with ulcerative colitis risk following maternal smoking exposure 4. Recent research identifies PRRT1 as an epigenetically regulated gene in Alzheimer's disease pathogenesis, with MAZ transcription factor controlling PRRT1 expression to mediate apoptosis and autophagy 5. Clinical significance: PRRT1 dysfunction may contribute to multiple neuropsychiatric and inflammatory conditions through altered AMPAR signaling and epigenetic mechanisms.