[7] SNAP-25, a Q-SNARE protein, is anchored to the cytosolic face of membranes via palmitoyl side chains covalently bound to cysteine amino acid residues in the central linker domain of the molecule.

SNAP-25 assembles with synaptobrevin and syntaxin-1, and the selective binding of these proteins enables vesicle docking and fusion to occur at active zones on the plasma membrane.

Random coil linker region with four cysteines clustered towards the center C-terminal α-helix Random coil linker region with four cysteines clustered towards the C-terminus C-terminal α-helix Minimal expression in adult tissue except in pituitary and adrenal gland tissues SNAP-25 not only plays a role in synaptogenesis and the exocytotic release of neurotransmitters, but it also affects spine morphogenesis and density, post synaptic receptor trafficking and neuronal plasticity.

[19][20] Individuals harboring pathogenic heterozygous de novo missense or loss-of-function variants in SNAP-25 often present with an early-onset developmental and epileptic encephalopathy.

The core symptoms comprise intellectual disability ranging between mild to profound and early-onset seizures mostly occurring before the age of two years.

[21] Electrophysiological studies identified aberrant spontaneous neurotransmission as causative and suggest that structurally clustered pathogenic variants lead to similar synaptic phenotypes.

An additional study indicated that incorporation of a SNAP-25 transgene back into the heterozygous SNAP-25 mutant mouse can rescue normal activity levels similar to wildtype mice.

The varying levels of SNAP-25 protein found in different areas of the brain have been thought to contribute to the conflicting psychological behaviors (depressive vs. hyperactive) expressed in some Schizophrenic patients.

[27][28][29][30] The blind-drunk (Bdr) mouse model which has a point mutations in the SNAP-25b protein has provided a complex phenotype involving behaviors such as an abnormal circadian rhythm,[31] uncoordinated gait, and disinterest in new objects/toys.

[33] Individuals with Alzhiemer's disease have been shown to have decreased presynaptic protein levels and impaired synaptic function in neurons.

[40] Certain polymorphisms of SNAP-25 (rs363043, rs353016, rs363039, rs363050) have been shown to affect the cognitive behavior, specifically the Intelligence Quotient (IQ)), of patients without pre-existing neurological diseases.

An additional study, showed that SNAP-25 levels in the hippocampus of the brain in neonatal mice were altered if the mother had been exposed to human influenza virus during pregnancy.