Investigators long inferred that cells stabilize intracellular pH (pH_i) in the face of a predicted passive H⁺ influx. In 1976, work with De Weer provided the first dynamic evidence of pH_i regulation: acid loaded with CO₂, squid axons exhibit a pH_i recovery toward normal. Introducing the NH₄-prepulse technique to acid load cells, we found that the pH_i recovery requires HCO₃. Work with Russell on axons, and by Thomas on snail neurons, identified the process as Na-driven Cl-HCO₃ exchange. In 1983, work with Boulpaep on renal tubules identified electrogenic Na/HCO₃ cotransport. In 1997, Romero et al expression cloned NBCe1 (Na/ HCO₃ cotransporter, electrogenic #1/SLC4A4), leading to the cloning of the other Na-coupled HCO₃ transporters (NCBTs) that play key roles in pH_i regulation and epithelial HCO₃ transport: NBCe2 (SLC4A5), NBCn1 (electroneutral #1/SLC4A7), NBCn2 (SLC4A10), and NDCBE (Na-driven Cl- HCO₃ exchanger/SLC4A8). Human NBCe1 mutations, first identified by Endou, cause severe renal-tubule acidosis and ocular, dental, and mental abnormalities. Genetic screens and mouse models associate other NCBT abnormalities with Usher 2B syndrome (NBCn1) and seizure susceptibility and autism (NBCn2). NBCe1 has a large cytosolic N terminus (Nt) that is dimeric in crystals, a large transmembrane domain with as many as 14 membrane spans, and a shorter cytosolic C terminus. Many NCBT-Nts contain an autoinhibitory domain whose effect is mooted when IRBIT binds to the Nt. We find that replacing the 4th extracellular loop of NBCe1 with that of NBCn1 converts the chimera to an electroneutral NBC. NBCn2 performs Cl-Cl exchange and in the absence of extracellular Cl^-, does Na-driven Cl- HCO₃ exchange. Under the same nonphysiological conditions, NDCBE does electroneutral Na/HCO₃ cotransport. We hypothesize that all SLC4s are in fact exchangers that sometimes masquerade as cotransporters.