Sodium-dependent phosphate transport protein 2B (SLC34A2) (SLC34A2)

Sodium-dependent phosphate transport protein 2B (SLC34A2), also known as NaPi-IIb, is a multi-pass transmembrane protein primarily expressed on the apical membrane of enterocytes in the small intestine. It is the major transporter responsible for active, sodium-dependent inorganic phosphate absorption from the diet, playing a crucial role in maintaining systemic phosphate balance. In the context of chronic kidney disease (CKD), impaired renal phosphate excretion leads to hyperphosphatemia, which is a significant risk factor for cardiovascular disease, vascular calcification, and bone disorders. Consequently, SLC34A2 has become a key therapeutic target for reducing intestinal phosphate uptake to manage serum phosphorus levels. While traditional phosphate binders act by sequestering phosphate in the gut lumen, novel small-molecule inhibitors like EOS789 and DS-2330 directly target SLC34A2 to block transcellular transport. The protein's activity is regulated by various factors, including dietary phosphate intake and 1,25-dihydroxyvitamin D3, which modulate its expression on the cell surface. Beyond active transport, the intestinal phosphate absorption process also involves a passive paracellular pathway, which is targeted by drugs such as tenapanor that inhibit the sodium-hydrogen exchanger 3 (NHE3). Clinical monitoring of therapies targeting this pathway involves measuring serum phosphate, fibroblast growth factor 23 (FGF23), and parathyroid hormone (PTH) levels. Safety concerns associated with inhibiting this transporter include gastrointestinal side effects, particularly diarrhea, and the potential for compensatory upregulation of other phosphate transporters.

Other names

NaPi-IIbNpt2bSodium/phosphate cotransporter 2BSolute carrier family 34 member 2Intestinal sodium-dependent phosphate transporter

Inhibition of the sodium-dependent phosphate cotransporter 2B (SLC34A2) to reduce active transcellular absorption of inorganic phosphate in the small intestine.