Dyn2-S848 phosphorylation serves as a molecular switch to promote endocytosis in muscle cells. Dyn2 activity is inhibited by the binding of Bin1 while GSK3α is inactivated by external signaling, e.g. insulin-PI3K-Akt. The attenuated endocytosis together with the increased exocytosis of GLUT4 lead to its efficient plasma membrane translocation and glucose uptake of muscle upon insulin stimulation. After insulin signaling turns off, GSK3α becomes active and phosphorylates Dyn2-S848 to relieve the Bin1 inhibition and promote endocytosis. The internalization of GLUT4 from muscle surface ceases the glucose uptake of skeletal muscle. CNM-related Bin1 mutations with partial truncation of the SH3 domain lose their inhibitory effect on Dyn2 thus resulting in hyperactive Dyn2 and fragmented T-tubule in muscle cells.