SLC4

SLC4, or solute carrier family 4, refers to a group of membrane transporters that mediate bicarbonate (HCO3−) and chloride exchange or sodium-bicarbonate cotransport across cell membranes. The family is commonly divided into two functional groups: the anion exchangers AE1–AE3, encoded by SLC4A1–SLC4A3, which exchange chloride for bicarbonate across the membrane; and the sodium-bicarbonate cotransporters NBCs, including members encoded by SLC4A4, SLC4A5, SLC4A7, and related genes, which co-transport sodium with bicarbonate. Within NBCs, the stoichiometry and tissue context determine whether the transporter is electrogenic or electroneutral.

SLC4 transporters are widely expressed across tissues. In red blood cells, they participate in CO2 transport by moving bicarbonate across the membrane. In the kidney, they mediate bicarbonate reabsorption and urinary acid-base balance; in the brain, pancreas, and intestine, they contribute to intracellular pH regulation and transepithelial bicarbonate movement. Proper function of SLC4 members is essential for maintaining systemic and cellular pH homeostasis and CO2 handling.

Structurally, SLC4 proteins are multi-pass membrane proteins with cytoplasmic regulatory regions; activity is modulated by cellular pH, CO2/bicarbonate levels, and signaling mechanisms. Some family members interact with cytoskeletal or regulatory proteins, and regulation can involve phosphorylation.

Clinical relevance: genetic alterations in SLC4 genes have been linked to human diseases, including red blood cell membrane disorders and renal or acid-base disturbances, although specific disease associations vary among members. Ongoing research aims to delineate isoform-specific roles and therapeutic implications.