The energy provided by NSF is transferred throughout the SNARE complex and SNAP, allowing the proteins to untangle, and recycled for future fusion events.

The function of SNAP proteins have been primarily related to the role which the play in the assemble and disassembly of SNARE complex required for vesicle fusion events.

According to the SNARE hypothesis developed in the early 1990s, SNAP protein are localized to the membranes and are central in mediating Ca2+ dependent vesicle fusion at these sites.

It is now understood that the 20S complex does not disassociate immediately following ATP hydrolysis, but rather remains tethered until intracellular Ca2+ achieve significantly high levels to facilitate docking.

Botulinum toxins do not directly interact with SNAP, but indirectly impact its ability to assemble into the 20S complex leading to impaired synaptic transmission at the neuromuscular junction.

Use of TEM and FRET imaging techniques was widely applied at the beginning of the century to resolve the SNARE complex and expanded to include SNAP proteins as well.

[13] The unwinding of the coiled-coil structures following ATP hydrolysis by NSF is also accompanied by a conformational change in syntaxin (SNARE) prior to vesicle fusion.

[5] Blocking of Sec17/SNAP interaction with SNAREs and Sec18/NSF has recently been reported in the literature using small molecules binding to PA (phosphatidic acid) to prevent priming activity and limit vesicle fusion.

In a studies of colorectal cancer of neuroendocrine markers, the expression of α-SNAP and β-SNAP were found to be higher in undifferentiated cells when compared to controls, and were associated with more aggressive disease.

[15] Similarly, expression of other vesicle trafficking proteins including synaptophysin, SNAP-25 (SNARE), VAMP2 and syntaxin-1 were also found to have various levels of increase small cell undifferentiated carcinomas.

[11] Aberrant of signaling and trafficking of proteins in cancer cells has been previously reported based on SNARE complex interactions for α-SNAP within implication of its role as a negative regulator of autophagy and the MAPK pathway thorough dephosphorylating.

[16] Depletion of α-SNAP has been reported to impair Golgi body integrity and assembly of vesicle fusion proteins at signaling junctions, while overexpression delays apoptosis in HeLa cells.

In a study of fetal brain development β-SNAP levels were found to be comparable between samples taken from Down syndrome (DS) affected and non-affected individuals.

The interaction of mutant huntingtin gene and vesicle fusion proteins may also be potentially responsible for deranged synaptic development or degeneration observed in the condition.

[7] Upregulation of α-SNAP was observed in mice with knock out 14-3-3 gamma protein suggesting a relationship between progression but not the pathogenesis of Creutzfeldt-Jakob Disease (CJD).

[21][7] Interaction of α-SNAP with AMPA receptors for glutamate may be potential target to improve synaptic plasticity through mechanism of stabilization at membranes where SNAPs are present.

Insufficiency in expression is indicated in a number of neurodegenerative and immune related conditions where the primary treatment strategy may focus on gene-therapy as replacement option.

Small molecule agents that can be used to block SNARE complex activity through interaction with SNAPs and have been used in vitro,[3] but their practical use may extend to in vivo systems as well.