 Based on sequence homology, the nine mammalian ClC proteins can be grouped into three classes, of which the first (ClC-1, ClC-2, ClC-Ka and ClC-Kb) is expressed primarily in plasma membranes, whereas the other two (ClC-3, ClC-4, and ClC-5 and ClC-6 and ClC-7) are expressed primarily in organellar membranes.ClC-5 is expressed in minor to moderate level in brain, muscle, intestine but highly in the kidney, primarily in proximal tubular cells of S3 segment, in alfa intercalated cells of cortical collecting duct of and in cortical and medullary thick ascending limb of Henle’s loop.Proximal tubular cells (PTCs) are the main site of ClC-5 expression.