The Role of the Endosomal Chloride/Proton Antiporter ClC-5 in Proximal Tubule Endocytosis and Kidney Physiology

The chloride channel (CLC) protein family comprises ion channels and proton-coupled anion transporters with fundamental physiological roles in humans. Several properties of CLC proteins defy the rigid dichotomy between ion channels and transporters as these opposite thermodynamic mechanisms of transport are implemented in a very similar structural architecture. All the CLC transporters are expressed in intracellular organelles where they are somehow important for the ionic homeostasis of these compartments. However, their specific physiological role is still unclear. This chapter focuses on the biophysical properties and physiological role of the endosomal Cl−/H+ antiporter ClC-5 mutated in Dent’s disease.