Sodium-dependent phosphate cotransporter 2A and Sodium-dependent phosphate cotransporter 2B (NaPi-2a/NaPi-2b)

The Sodium-dependent phosphate cotransporter 2A (NaPi-2a, SLC34A1) and 2B (NaPi-2b, SLC34A2) are integral membrane proteins belonging to the SLC34 solute carrier family, essential for maintaining systemic phosphate homeostasis. NaPi-2a is primarily localized to the apical membrane of the renal proximal tubule, where it mediates the majority of filtered phosphate reabsorption from the urine. NaPi-2b is predominantly expressed in the small intestine, facilitating the absorption of dietary phosphate, and is also found in the lungs and other tissues. Dysregulation of these transporters is associated with hyperphosphatemia in chronic kidney disease (CKD), while genetic mutations can lead to nephrolithiasis (NaPi-2a) or pulmonary alveolar microlithiasis (NaPi-2b). In oncology, NaPi-2b is recognized as a tumor-associated antigen overexpressed in ovarian and lung cancers, serving as a target for antibody-drug conjugates (ADCs) designed to deliver cytotoxic agents directly to malignant cells. Pharmacological strategies include small-molecule inhibitors to manage phosphate levels in CKD and ADCs for targeted cancer therapy.

Other names

SLC34A1SLC34A2Npt2aNpt2bNaPi-IIaNaPi-IIbSodium-phosphate cotransporter type IIaSodium-phosphate cotransporter type IIbSolute carrier family 34 member 1Solute carrier family 34 member 2

Inhibition of sodium-dependent phosphate transport in the kidney (NaPi-2a) and intestine (NaPi-2b) to reduce phosphate reabsorption and absorption, respectively, thereby lowering serum phosphate levels. In oncology, NaPi-2b-targeted antibody-drug conjugates (ADCs) bind to the transporter on the surface of cancer cells to deliver cytotoxic payloads.