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Detailed structural information is available from crystal structures of bacterial and algal CLCs. Mammals express nine CLC genes, four of which encode Cl<jats:sup>\u2013<\/jats:sup>channels and five 2Cl<jats:sup>\u2013<\/jats:sup>\/H<jats:sup>+<\/jats:sup>\u2010exchangers. Two accessory \u03b2\u2010subunits are known: (1) barttin and (2) Ostm1. ClC\u2010Ka and ClC\u2010Kb Cl<jats:sup>\u2013<\/jats:sup>channels need barttin, whereas Ostm1 is required for the function of the lysosomal ClC\u20107 2Cl<jats:sup>\u2013<\/jats:sup>\/H<jats:sup>+<\/jats:sup>\u2010exchanger. ClC\u20101, \u20102, \u2010Ka and \u2010Kb Cl<jats:sup>\u2013<\/jats:sup>channels reside in the plasma membrane and function in the control of electrical excitability of muscles or neurons, in extra\u2010 and intracellular ion homeostasis, and in transepithelial transport. The mainly endosomal\/lysosomal Cl<jats:sup>\u2013<\/jats:sup>\/H<jats:sup>+<\/jats:sup>\u2010exchangers ClC\u20103 to ClC\u20107 may facilitate vesicular acidification by shunting currents of proton pumps and increase vesicular Cl<jats:sup>\u2013<\/jats:sup>concentration. ClC\u20103 is also present on synaptic vesicles, whereas ClC\u20104 and \u20105 can reach the plasma membrane to some extent. ClC\u20107\/Ostm1 is coinserted with the vesicular H<jats:sup>+<\/jats:sup>\u2010ATPase into the acid\u2010secreting ruffled border membrane of osteoclasts. Mice or humans lacking ClC\u20107 or Ostm1 display osteopetrosis and lysosomal storage disease. Disruption of the endosomal ClC\u20105 Cl<jats:sup>\u2013<\/jats:sup>\/H<jats:sup>+<\/jats:sup>\u2010exchanger leads to proteinuria and Dent's disease. Mouse models in which ClC\u20105 or ClC\u20107 is converted to uncoupled Cl<jats:sup>\u2013<\/jats:sup>conductors suggest an important role of vesicular Cl<jats:sup>\u2013<\/jats:sup>accumulation in these pathologies. The important functions of CLC Cl<jats:sup>\u2013<\/jats:sup>channels were also revealed by human diseases and mouse models, with phenotypes including myotonia, renal loss of salt and water, deafness, blindness, leukodystrophy, and male infertility. \u00a9 2012 American Physiological Society.<jats:italic>Compr Physiol<\/jats:italic>2:1701\u20101744, 2012.<\/jats:p>","DOI":"10.1002\/cphy.c110038","type":"other","created":{"date-parts":[[2012,6,26]],"date-time":"2012-06-26T23:26:21Z","timestamp":1340753181000},"page":"1701-1744","source":"Crossref","is-referenced-by-count":120,"title":["Cell Biology and Physiology of CLC Chloride Channels and Transporters"],"prefix":"10.1002","author":[{"given":"Tobias","family":"Stauber","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Weinert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas 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