•  ClC‐5 is a 2Cl−/1H+ antiporter expressed in endosomes that is essential for proper endocytosis, but its molecular function is still not understood. •  In heterologous systems ClC‐5 elicits currents only at positive potentials. This rectifying behaviour conflicts with most of the models proposed to explain ClC‐5 function. The origin of this rectification is unknown. •  Here we identified a ClC‐5 mutation, D76H, that elicits inward tail currents at negative potentials. •  These currents reflect transmembrane transport that preserve the 2Cl−/1H+ stoichiometry. •  We conclude that a gating mechanism regulates ClC‐5 transport activity and is at least in part responsible for the strong rectification of ClC‐5 currents. Abstract  ClC‐5 is a 2Cl−/1H+ antiporter highly expressed in endosomes of proximal tubule cells. It is essential for endocytosis and mutations in ClC‐5 cause Dent's disease, potentially leading to renal failure. However, the physiological role of ClC‐5 is still unclear. One of the main issues is whether the strong rectification of ClC‐5 currents observed in heterologous systems, with currents elicited only at positive voltages, is preserved in vivo and what is the origin of this rectification. In this work we identified a ClC‐5 mutation, D76H, which, besides the typical outward currents of the wild‐type (WT), shows inward tail currents at negative potentials that allow the estimation of the reversal of ClC‐5 currents for the first time. A detailed analysis of the dependence of these inward tail currents on internal and external pH and [Cl−] shows that they are generated by a coupled transport of Cl− and H+ with a 2 : 1 stoichiometry. From this result we conclude that the inward tail currents are caused by a gating mechanism that regulates ClC‐5 transport activity and not by a major alteration of the transport mechanism itself. This implies that the strong rectification of the currents of WT ClC‐5 is at least in part caused by a gating mechanism that activates the transporter at positive potentials. These results elucidate the biophysical properties of ClC‐5 and contribute to the understanding of its physiological role.