Hypokalemia is a common and incompletely explained finding in distal renal tubular acidosis (dRTA); its severity depending on the cause. Hereditary dRTA can be due to mutations in the anion exchanger 1 (AE1, Band 3). Recent work has shown that AE1 mutations associated with hereditary stomatocytosis (HSt) – an erythrocyte defect that can be a cause of pseudohyperkalemia – can behave as non-selective cation channels¹. To investigate whether dRTA-causing AE1 mutants could also contribute to renal potassium wasting in dRTA via a similar mechanism, we studied 3 European autosomal dominant dRTA-causing mutants (R589H, G609R, S613F) and one Thai autosomal recessive mutant (G701D); each co-expressed with glycophorin A (GPA – to enhance plasma membrane expression) in Xenopus Laevis oocytes. Chloride influx experiments showed that anion transport activity is preserved and similar to wild type (wt), in contrast to the cation leaky HSt mutants described previously. However, rubidium (Rb⁺) influx experiments showed significantly higher cation flux in the western mutants compared with wt. Moreover, G701D had a very large cation flux, which was greatest at 0^oC and was inhibited by stilbene AE1 inhibitors. These results were confirmed by measurement of intracellular cations: mutant-expressing oocytes, notably G701D, had reversal of intracellular cation concentrations compared with wt. In addition, when G701D was co-expressed with wt AE1 in the absence of GPA, a strong Rb⁺ flux was still found, indicating stability of the cation channel with heterodimer formation. The G701D mutation is particularly frequent in NE Thailand², where dRTA and severe hypokalemia are endemic³, and hypokalemic paralysis, and sudden death, are unusually common^4,5. The novel behaviour of the AE1 mutants we have observed may contribute to potassium wasting in G701D homo and heterozygotes and thus add to the burden of hypokalemic disease seen in NE Thailand.