SYN1 (synapsin I) is a neuronal phosphoprotein that coats synaptic vesicles and binds to the cytoskeleton, serving as a critical regulator of synaptic vesicle trafficking and neurotransmitter release at presynaptic terminals 1. The protein functions as a cytoskeletal protein-membrane anchor that coordinates synaptic vesicle clustering and exocytosis, thereby controlling chemical synaptic transmission efficiency 2. SYN1 also participates in axon outgrowth and synaptogenesis regulation, with evidence suggesting involvement in nitric oxide signaling through interaction with NOS1 and CAPON proteins at presynaptic sites. Pathogenic SYN1 variants cause X-linked epilepsy characterized by a distinctive electroclinical phenotype, primarily manifesting reflex seizures triggered by cutaneous water contact or defecation, with temporo-perisylvian seizure semiology 3. Affected individuals frequently present developmental delay and behavioral disorders alongside epilepsy 1. Functional connectivity analysis reveals increased temporal lobe connectivity and a shift toward lower-frequency EEG bands in SYN1-related epilepsy 3. Therapeutically, lamotrigine, lacosamide, carbamazepine, and oxcarbazepine demonstrate superior seizure control compared to valproic acid and levetiracetam in this syndrome, with sodium channel blockers emerging as the optimal treatment strategy 4. Additionally, SYN1 expression serves as a synaptic plasticity biomarker, with reduced levels observed in gliomas and depression-associated conditions 56.