Potassium-chloride cotransporters (KCCs) are members of the cation chloride cotransporter gene (Slc) superfamily. This family consists of sodium-potassium-two chloride cotransporter 1 (NKCC1) and 2 (NKCC2), sodium-chloride cotransporter (NCC) and KCCs¹. All of these transporters mediate electroneutral transport of cations coupled with one or two Cl^- ions and contribute to regulation of cell volume and homeostasis of intracellular Cl^- concentration. KCCs extrude one K⁺ with one Cl^- from the intracellular space to the extracellular space by using the chemical gradient of K⁺ as the driving force².

Four KCC isoforms (KCC1, KCC2, KCC3 and KCC4) have been identified in mammalian species³.

K-Cl cotransporters regulate neuronal and glial electrochemical equilibrium potential for Cl^-, and so can determine the excitatory or inhibitory influences of GABA- and glycine-gated Cl^- channels⁴. KCC1 is a member of the cation-chloride cotransporter (CCC) superfamily of proteins, as with all CCC proteins, KCC1 is an integral membrane protein with 12 transmembrane domains and both N- and C-terminal cytoplasmic domains ⁵. KCC1 is ubiquitously expressed⁶.

K-Cl cotransport activity is elevated in red blood cells of individuals with sickle cell disease, thalassemia, and diseases associated with other mutant Hb. Human erythrocytes from individuals with the reticulocytotic anemic states of sickle cell disease, Hb SC disease, and β-thalassemia intermedia exhibit uniformly elevated KCC1-like immunoreactivity compared with normal AA erythrocytes⁷.