Metabolic reprograming is a process in which cells alter their biosynthetic and bioenergetic pathways to meet the changing energetic demands. To ensure energy supply, cancer cells increase glucose uptake and adapt their glucose metabolism from oxidative phosphorylation to aerobic phosphorylation. Metabolic reprograming towards aerobic glycolysis is also required for angiogenesis, as angiogenesis happens in tissues that in need of more blood (oxygen) supply. Although aerobic glycolysis was originally identified by Warburg nearly century ago, the molecular mechanisms regulating aerobic glycolysis remain elusive. In this issue of Cell death & disease (14, 183 (2023)), Wu and colleagues identified that by regulating calcineurin-CRTC2-CREB signaling pathway, TRPM7-mediated Ca2+ influx promotes the expression of glucose transporter 3 (GLUT3), which is needed for the programming of energy metabolism from oxidative phosphorylation toward aerobic glycolysis during tumorigenesis and angiogenesis. This study highlights the critical role of TRPM7 in metabolic reprogramming, and suggests that TRPM7 can be a molecular target for the treatment of other metabolic reprograming-related diseases.