The SLC4A4 gene encodes the Na+-HCO3? co-transporter (NBC), which is involved in the regulation of bicarbonate secretion and absorption and intracellular pH. There is the kidney-type transporter (kNBC1) and the pancreatic-type transporter (pNBC1). kNBC1 plays an important role in bicarbonate absorption from renal proximal tubules, whilst pNBC1 is involved in bicarbonate secretion from pancreatic duct cells.

SLC4A4 is also widely expressed in several ocular tissues, such as the corneal endothelium, trabecular meshwork, pigmented and nonpigmented ciliary epithelium, and lens epithelium. Three transcripts are encoded by the SLC4A4 gene.

The SLC4A4 gene spans approximately 450 kB and contains 26 exons. Exon 1 is specific to the pNBC1 transcript; while kNBC1 is transcribed from alternative promoters in intron 3.

Loss-of-function (mostly missense) mutations in the SLC4A4 gene can cause proximal renal tubular acidosis (pRTA) with ocular abnormalities. Based on functional studies it was concluded that at least 50% reduction of SLC4A4 activity is required for the disease to occur.