SNCA encodes α-synuclein, a neuronal protein with multifaceted roles in synaptic function and neurotransmission. As a monomer, α-synuclein enhances synaptic vesicle priming, fusion, and exocytotic pore dilation by increasing local Ca²⁺ release from microdomains 1. In its multimeric membrane-bound state, it functions as a molecular chaperone assisting SNARE complex assembly at the presynaptic membrane, critical for maintaining normal fusion during aging 2. α-synuclein also modulates dopamine neurotransmission by regulating dopamine transporter activity 3. Pathologically, SNCA mutations, duplications, and polymorphisms cause or increase risk for Parkinson disease (PD) and related synucleinopathies 45. Intracellular α-synuclein accumulation is a hallmark of these disorders, with protein aggregates forming Lewy bodies and Lewy neurites 4. Disease-modifying therapeutic approaches target α-synuclein reduction through antisense oligonucleotides 6, enhanced lysosomal degradation via cathepsin D 7, autophagy enhancement 8, and PLK2 inhibition to restore autophagic clearance 9. SNCA overexpression shows sex- and gene-dose-dependent effects on neurodegeneration 10, with males exhibiting more pronounced pathology.