SLC4A9 encodes an electroneutral chloride/bicarbonate antiporter located on chromosome 5 1. The protein mediates Cl⁻/HCO₃⁻ exchange coupled with monovalent cations (Na⁺, K⁺, Cs⁺, Li⁺, Rb⁺) across the basolateral membrane 2. In the kidney, AE4 (the SLC4A9 protein product) functions as a critical acid-base sensor in intercalated cells, enabling appropriate physiological responses to metabolic acidosis and alkalosis by regulating pendrin-mediated base secretion 3. SLC4A9 expression is predominantly restricted to the kidney and increases under hypoxic conditions in cancer cells 1, 4. In adenocarcinoma and glioma models, SLC4A9 disruption acidifies intracellular pH and suppresses tumor growth, suggesting therapeutic potential 4. Recent genome-wide association studies identified SLC4A9 as a candidate Alzheimer disease risk gene; experimental rescue of SLC4A9 expression proved neuroprotective in Drosophila AD models, with potential implications for tau pathology 5. DNA methylation changes at SLC4A9 show association with all-cause mortality in cardiovascular patients 6. SLC4A9 likely participates in broader pH homeostasis networks alongside other SLC4 family members 7.