This handbook on vacuolar and plasma membrane H+-ATPases is the first to focus on an essential link between vacuolar H+-ATPase and the glycolysis metabolic pathway to understand the mechanism of diabetes and the metabolism of cancer cells. It presents recent findings on the structure and function of vacuolar H+-ATPase in glucose promoting assembly and signaling, in addition to describing the regulatory mechanisms of vacuolar H+-ATPase in yeast cells, neural stem cells, kidney cells, cancer cells, as well as under diabetic conditions.