Anion exchanger 1: Protean function and associations

Anion exchanger 1 (AE1) is the most abundant protein on the erythrocyte membrane and is also present on the basolateral surface of the alpha intercalated cell in the distal nephron. Mutations can cause either hereditary haemolytic red cell diseases, or hereditary distal renal tubular acidosis. Classically it mediates the electroneutral exchange of chloride for bicarbonate, as well as comprising an important mechanical component of the red cell membrane. It is increasingly recognised that it plays many other roles too: alternative anion transport, such as sulphate transport and proton and sulphate symport, associations with other erythrocyte membrane proteins as part of the AE1 macrocomplex, regulation of glycolysis and more recently cation transport through the so-called ‘leak’ pathway. These new functions and associations are reviewed in health and disease, and the role of AE1 as a putative regulator of cell volume is discussed.