In nature, chlorine is most abundant as a chloride ion. Physiologically, it exists as an ion in the body. The chloride ion is an essential anion that the body needs for many critical functions. Chloride is a prominent negatively charged ion of the blood, where it represents 70% of the body’s total negative ion content. On average, an adult human body contains approximately 115 grams of chloride, making up about 0.15% of total body weight. The suggested amount of chloride intake ranges from 750 to 900 milligrams per day, based on the fact that total obligatory loss of chloride in the average person is close to 530 milligrams per day. Chloride helps keep the body's acid-base balance. The amount of chloride in the blood is carefully controlled by the kidneys. In addition to its functions as an electrolyte, chloride combines with hydrogen in the stomach to make hydrochloric acid, a powerful digestive enzyme that is responsible for the break down of proteins, absorption of other metallic minerals, and activation of intrinsic factor, which in turn absorbs vitamin B12. Chloride ions also have other important physiological roles. For instance, in the central nervous system, the inhibitory action of glycine and some of the action of GABA relies on the entry of Cl- into specific neurons. Also, the chloride-bicarbonate exchanger biological transport protein relies on the chloride ion to increase the blood's capacity of carbon dioxide, in the form of the bicarbonate ion. Chloride-transporting proteins (CLC) play fundamental roles in many tissues in the plasma membrane as well as in intracellular membranes. CLC proteins form a gene family that comprises nine members in mammals, at least four of which are involved in human genetic diseases. GABA(A) receptors are pentameric complexes that function as ligand-gated chloride ion channels. WNK kinases are a family of serine-threonine kinases that have been shown to play an essential role in the regulation of electrolyte homeostasis, and they are found in diverse epithelia throughout the body that are involved in chloride ion flux. Cystic fibrosis (CF) is caused by alterations in the CF transmembrane conductance regulator (CFTCR) gene that result in deranged sodium and chloride ion transport channels. (A7709, A7710, A7711, A7712, A11065).