Five mammalian members of the CLC family of chloride channels and transporters,C1C-3 through ClC-7, are predominantly expressed on vesicles of the endoso-mal-lysosomal system.They were previously thought to be chloride channels (like C1C-1,-2,-Ka and-Kb) and their role was seen in providing countercurrents for electrogenic vesicular proton pumps.Without such neutralizing currents these H+-ATPases would not be able to acidify the cell interior.