Understanding the Physiological Role of Electroneutral Na(+)-Coupled HCO(3)(−) Cotransporter and Its Therapeutic Implications

Acid–base homeostasis is critical for proper physiological function and pathology. The SLC4 family of HCO(3)(−) transmembrane cotransporters is one of the HCO(3)(−) transmembrane transport carriers responsible for cellular pH regulation and the uptake or secretion of HCO(3)(−) in epithelial cells. NBCn1 (SLC4A7), an electroneutral Na(+)/HCO(3)(−) cotransporter, is extensively expressed in several tissues and functions as a cotransporter for net acid extrusion after cellular acidification. However, the expression and activity level of NBCn1 remain elusive. In addition, NBCn1 has been involved in numerous other cellular processes such as cell volume, cell death/survival balance, transepithelial transport, as well as regulation of cell viability. This review aims to give an inclusive overview of the most recent advances in the research of NBCn1, emphasizing the basic features, regulation, and tissue-specific physiology as well as the development and application of potent inhibitors of NBCn1 transporter in cancer therapy. Research and development of targeted therapies should be carried out for NBCn1 and its associated pathways.