NSF unravels SNARE complexes once membrane fusion has occurred, using the hydrolysis of ATP as an energy source, allowing the dissociated SNAREs to be recycled for reuse in further rounds of membrane fusion.

Thus, conditional temperature-sensitive mutations in the Drosophila melanogaster gene for NSF lead to a comatose behaviour at the restrictive temperature (and hence the gene is called comatose), presumably because neuronal functions are blocked.

In Dictyostelium discoideum amoebae, similar mutations lead to a cessation of cell movement at the restrictive temperature, indicating a role for intracellular membrane transport in migration.

This gives NSF a putative role in delivery and expression of AMPA receptors at the synapse.

[11] NSF was discovered by James Rothman and colleagues in 1987 while at Stanford University; they identified NSF after observing that a cytoplasmic factor, required for membrane fusions, was inactivated by treatment with N-ethylmaleimide.