Bedaquiline (BDQ), an inhibitor of the mycobacterial FF-ATP synthase, has revolutionized the antitubercular drug discovery program by defining energy metabolism as a potent new target space. Several studies have recently suggested that BDQ ultimately causes mycobacterial cell death through a phenomenon known as uncoupling. The biochemical basis underlying this, in BDQ, is unresolved and may represent a new pathway to the development of effective therapeutics. In this communication, we demonstrate that BDQ can inhibit ATP synthesis in by functioning as a H/K ionophore, causing transmembrane pH and potassium gradients to be equilibrated. Despite the apparent lack of a BDQ-binding site, incorporating the F subunit into liposomes enhanced the ionophoric activity of BDQ. We discuss the possibility that localization of BDQ at FF-ATP synthases enables BDQ to create an uncoupled microenvironment, by antiporting H/K Ionophoric properties may be desirable in high-affinity antimicrobials targeting integral membrane proteins.