Publisher Summary This chapter provides an overview of the potassium-chloride (K+-Clˉ) cotransporters. These cotransporters are carrier proteins that mediate the coupled, electroneutral transport of one K+ ion and one Clˉ ion across the plasma membrane. This coupled transport is obligatory as it absolutely requires the simultaneous presence of both K+ and Clˉ ions on the same side of the membrane for net transport to proceed. The K+-Clˉ cotransporters are members of a larger gene family called the cation-chloride cotransporters (CCCs) or solute carrier family 12 (SLC12). This gene family also includes the Na+-K+-Clˉ cotransporter (NKCC) and the Na+-Clˉ cotransporter (NCC). The chapter also defines the molecular biology of the cation-chloride cotransporter gene family, the K+-Clˉ cotransporters exhibit the greatest genetic diversity. Four distinct isoforms of the K+-Clˉ cotransporter are identified, KCC1 (Slc12a4), KCC2 (Slc12a5), KCC3 (Slc12a6), and KCC4 (Slc12a7). Additionally, these KCC isoforms exhibit alternative exon splicing and the use of alternative promoters and first exons, leading to an even greater diversity.