Vamp1, also known as vesicle-associated membrane protein 1, is crucial for synaptic exocytosis. It mediates GABA release probability from parvalbumin-expressing interneurons (PVIs) and is a major target of cytoplasmic RNA binding fox-1 homolog 1 (Rbfox1) [2,3]. Mutations in Vamp1 are associated with congenital myasthenic syndrome-25 (CMS-25), an autosomal recessive neuromuscular disorder [1]. Additionally, it has been linked to dominant hereditary spastic ataxia in some families [4].

Mutations in Vamp1 have been studied in human patients. Homozygous mutations in Vamp1 cause CMS-25, presenting symptoms such as motor developmental delay, hypotonia, muscle weakness, and various associated complications like strabismus, ptosis, and recurrent nephrolithiasis [1]. In schizophrenia patients, the Rbfox1-Vamp1 pathway in PVIs of the prefrontal cortex is impaired, with lower cytoplasmic Rbfox1 protein levels leading to reduced Vamp1 mRNA levels, contributing to deficient gamma power in the illness [2,3].

In conclusion, Vamp1 plays a vital role in synaptic exocytosis and GABA release. Studies on human mutations associated with Vamp1 have revealed its significance in neuromuscular and neurological disorders, such as CMS-25 and schizophrenia. Understanding the function of Vamp1 provides insights into the underlying mechanisms of these diseases, potentially guiding future treatment strategies.