RPH3A encodes rabphilin 3A, a synaptic protein with dual presynaptic and postsynaptic functions. Presynaptically, RPH3A is recruited to synaptic vesicle membranes by RAB3A in a GTP-dependent manner to modulate vesicle trafficking and calcium-triggered neurotransmitter release 1. Postsynaptically, RPH3A stabilizes GluN2A-containing NMDA receptors at the cell surface through phase separation mechanisms and forms a ternary complex with GRIN2A and DLG4, which is essential for synaptic plasticity and cognition 2. RPH3A also regulates neutrophil polarization through interaction with phosphatidylinositol-4-phosphate and ARF6, facilitating immune cell adhesion 3. Pathogenic RPH3A missense variants cause neurodevelopmental disorders with variable clinical presentations. Variants exhibit gain-of-function effects, increasing GluN2A-containing NMDA receptors at extrasynaptic sites and altering synaptic function 1. Disease manifestations range from drug-resistant epilepsy with intellectual disability to autism spectrum disorder 1, 4. RPH3A variants impair both presynaptic glutamate release and postsynaptic NMDAR retention, reducing calcium signaling at dendritic spines 4. RPH3A is identified as a congenital myasthenic syndrome gene 5 and represents a therapeutic target for levodopa-induced dyskinesias through modulation of striatal GluN2A composition 6.