Mutations in the electrogenic Na+/HCO3 cotransporter (NBCe1) that cause pRTA, glaucoma and cataracts in patients are recessive. Parents and siblings of these affected individuals seem asymptomatic though their tissues should make some mutant NBCe1 protein. Biochemical studies with AE1 and NBCe1 indicate that both Slc4 members form dimers. However, the physiologic implications of dimerization have not yet been fully explored. Here, human NBCe1A dimerization is demonstrated by biomolecular fluorescence complementation (BiFC). An EYFP fragment (1-158, EYFPN) or (159-238, EYFPC) was fused to the N- or C-terminus of NBCe1A and mix-and-matched expressed in Xenopus oocyte. The EYFP fluorescent signal was observed only when both EYFP fragments are fused to the N-terminus of NBCe1A (EYFPN-N-NBCe1A w/ EYFPC-N-NBCe1A) and the electrophysiology data demonstrated this EYFP-NBCe1A co-expressed pair have WT transport function. These data suggest NBCe1A forms dimers and that N-termini from the two monomers are in close proximity, likely pair up, to form a functional unit. To explore the physiologic significance of NBCe1 dimerization, we chose two severe NBCe1 mutations (6.6 and 20% WT function individually): S427L (naturally occurring) and E91R (for N-terminal structure studies). When we co-expressed S427L and E91R, we measured 50% wild type function which can only occur if the S427L-E91R heterodimer is the functional unit. We hypothesize that the dominant negative effect of heterozygous NBCe1 carrier should be obvious if the mutated residues are structurally crucial to the dimer formation. The S427L-E91R heterodimer complex allows the monomers to structurally complement each other resulting in a dimer with wild-type like function.