Cover: V-ATPases are ATP-dependent proton pumps that both acidify intracellular compartments and pump protons across the plasma membrane of eukaryotic cells. They have been implicated in the survival, drug resistance, signaling, and invasiveness of tumor cells, making them an attractive and novel target in the development of therapeutics to limit tumor growth and metastasis. Model adapted from Couoh-Cardel et al. (J Biol Chem 2015). See Stransky, Laura, Kristina Cotter, and Michael Forgac. Physiol Rev 96: 1071–1091, 2016.