The idea of localised ATP supply or an ATP microdomain is controversial63 because in most cells, global ATP concentration is always well above the saturating concentration for most ATP-dependent processes, including the PMCA.64,65 However, such a privileged ATP supply to the PMCA may become critical when ATP synthesis is compromised, for example during severe hypoxia, or in cancer cells that exhibit impaired mitochondrial ATP production or express dimeric PKM2 with low catalytic activity. The gene discussed is PKM; the disease is cancer.