The electrogenic Na+-HCO3
- cotransporter NBC1, also known as NBCe1, is expressed in several tissues such as
kidney, pancreas, eye, and brain. NBC1 has three variants, which may mediate different physiological functions. Inactivating
mutations in NBC1 result in proximal renal tubular acidosis associated with ocular abnormalities. Functional
analysis suggests that at least 50% reduction in NBC1 activity is required to induce severe acidemia invariably associated
with stunted growth. Some mutations in the NBC1 gene may also induce trafficking abnormalities. On the other hand, the
variant-specific N-terminal regions seem to play an essential role in the full activation of NBC1. This review will focus on
the recent progress in physiology and pathophysiology of NBC1.