Vesicle-fusing ATPase

NSF (Vesicle-fusing ATPase) is an AAA-family ATPase essential for intracellular membrane trafficking. It catalyzes the fusion of transport vesicles within the Golgi cisternae and facilitates cargo delivery from the endoplasmic reticulum to the Golgi stack. NSF also interacts with the AMPAR subunit GRIA2 to influence its membrane cycling (UniProt: P46459).

NSF is broadly expressed across cellular compartments involved in vesicular transport. In addition to its roles in general secretory pathways, NSF participates in synaptic plasticity through regulation of AMPA receptor trafficking—a process critical for learning and memory. A heterozygous loss-of-function variant in NSF causes Developmental and Epileptic Encephalopathy 96 (DEE96; MIM 619340), characterized by early-onset refractory seizures and neurodevelopmental impairment (UniProt: P46459).

NSF levels are significantly reduced in Alzheimer's disease. Chaparral AD proteomics data from post-mortem AD brain tissue (TMT-labeled DDA proteomics across four subcellular fractions) show NSF is downregulated relative to age-matched controls, with a mean log2 fold-change of −0.55 (Chaparral AD proteomics). This reduction may compromise vesicular trafficking and synaptic AMPAR cycling, processes implicated in AD-related cognitive decline.