, while reducing inhibition of both exchange mechanisms by acid pHo. The E699Q mutation also leads to increased potency of selfinhibition by extracellular SO 4 2Ϫ . Study of the Ae1 E699Q mutation has revealed the existence of a novel pH-regulatory site of the Ae1 polypeptide and should continue to provide valuable paths toward understanding substrate selectivity and self-inhibition in SLC4 anion transporters. band 3; 4,4Ј-diisothiocyanostilbene-2,2Ј-disulfonic acid; Xenopus oocyte; Woodward's reagent K THE SLC4 BICARBONATE TRANSPORTER superfamily encodes Na ϩ -dependent and Na ϩ -independent anion carriers (3,30,32,44). SLC4A1/AE1/band 3 is the most thoroughly studied among the Na ϩ -independent, electroneutral Cl Ϫ /HCO 3 Ϫ exchangers. AE1 is the major intrinsic protein of the erythrocyte membrane, where it serves to increase the total CO 2 -carrying capacity of the blood (48). The kidney variant of AE1 is expressed in the basolateral membrane of the renal type A intercalated cell. AE1 mutations cause dominant hereditary spherocytosis, stomatocytosis, and ovalocytosis, and a distinct set of mutations cause dominant and recessive forms of distal renal tubular acidosis (2, 24).In