SNAP-25 (synaptosomal-associated protein of 25 kDa) is a plasma membrane protein that, together with syntaxin and the synaptic vesicle protein VAMP/synaptobrevin, forms the SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) docking complex for regulated exocytosis. SNAP-25 also modulates different voltage-gated calcium channels, representing therefore a multifunctional protein that plays essential roles in neurotransmitter release at different steps. Recent genetic studies of human populations and of some mouse models implicate alterations in SNAP-25 gene structure, expression, and/or function in contributing directly to these distinct neuropsychiatric and neurological disorders.