The findings of this study not only provide a new understanding of the functional regulation of RNF213 and Cav-1 and their effects on NO release in endothelial cells, but also give insights into how disruption of these processes by MMD-related mutations, such as R4810K, can lead to abnormal signaling events that contribute to endothelial cell dysfunction, altered vascular remodeling, and MMD pathogenesis. This evidence concerns the gene RNF213 and multiminicore myopathy.