 Environment acidification is necessary for the dissociation of ligand from its receptor.The receptor is then recycled to the apical membrane, while ligand is transported to the late endosome and lysosome where it is degraded.ClC-5 supports efficient acidification of endosomes either by providing a Cl− conductance to counterbalance the accumulation of positively charged H+ pumped in by V-ATPase or by directly acidifying endosome in parallel with V-ATPase.