Scamp5, a member of the secretory carrier membrane protein family, is highly expressed in the brain. It participates in membrane transport, regulating exocytosis and endocytosis of synaptic vesicles (SVs), and is crucial for maintaining normal nerve cell physiological functions. It is also related to secretion carrier and membrane function [1].

In genetic models, Scamp5-deficient models have provided insights. For instance, Scamp5 R91W mutant knock-in mice show early-onset epilepsy similar to human pediatric epilepsy cases. The mutation affects the interaction between Scamp5 and synaptotagmin 1, dysregulating neurotransmitter release and shifting the excitation/inhibition balance in the neuronal network [3]. Additionally, knockdown of Scamp5 in cultured rat hippocampal neurons reduces the total and recycling vesicle pool sizes, slows endocytosis, and impairs it during strong stimulation, suggesting its role in high neuronal activity [2].

In conclusion, Scamp5 is essential for synaptic function, with its disruption leading to neurological disorders such as epilepsy. Mouse models, especially those with loss-of-function mutations or knockdown, have been instrumental in revealing its role in regulating neurotransmitter release and synaptic vesicle dynamics, providing a better understanding of the pathogenesis of related neurological diseases.