[5] A loss of NCC function causes Gitelman syndrome, an autosomic recessive disease characterized by salt wasting and low blood pressure, hypokalemic metabolic alkalosis, hypomagnesemia and hypocalciuria.

The sodium-chloride symporter's protein sequence has a high degree of identity between different mammalian species (over 90% between human, rat and mouse).

N-glycosylation occurs in two sites in a long extracellular loop connecting two transmembrane domains within the hydrophobic core.

NCC activity is known to have two control mechanisms affecting protein trafficking to the plasma membrane and transporter kinetics by phosphorylation and de-phosphorylation of conserved serine/threonine residues.

[5] A loss of NCC function is associated with Gitelman syndrome, an autosomic recessive disease characterized by salt wasting and low blood pressure, hypokalemic metabolic alkalosis, hypomagnesemia and hypocalciuria.

[13] Type II mutations cause a partial loss of NCC function in which the cotransporter is trafficked to the cell surface but has an impaired insertion in the plasma membrane.

NCC harboring type II mutations have normal kinetic properties but are present in lower amounts at the cell surface, resulting in a decreased uptake of sodium and chloride.