Sodium-dependent phosphate transport protein 2B (NaPi-2b) (NaPi-2b)

Sodium-dependent phosphate transport protein 2B, also known as NaPi-2b or SLC34A2, is a multi-transmembrane protein belonging to the solute carrier family 34. It functions as an electrogenic symporter, moving three sodium ions with one divalent phosphate ion across the apical membrane of epithelial cells [13, 17]. Its primary physiological roles include mediating the majority of dietary phosphate absorption in the small intestine and regulating phosphate levels in the lungs by clearing phosphate released during surfactant recycling in type II alveolar cells [4, 6]. Genetic loss-of-function mutations in the SLC34A2 gene lead to pulmonary alveolar microlithiasis, a rare condition involving the accumulation of calcium phosphate microliths in the lung alveoli [6, 13]. In therapeutic development, NaPi-2b is a prominent target for both oncology and nephrology. It is highly overexpressed in certain malignancies, particularly high-grade serous ovarian cancer and lung adenocarcinoma, while maintaining restricted expression in most normal tissues [5, 8, 21]. This expression profile has led to the development of several NaPi-2b-targeting antibody-drug conjugates (ADCs), such as upifitamab rilsodotin and lifastuzumab vedotin, designed to deliver cytotoxic payloads directly to tumor cells [9, 11, 15]. Additionally, small-molecule inhibitors of intestinal NaPi-2b are being investigated as potential treatments for hyperphosphatemia in chronic kidney disease (CKD) to reduce systemic phosphate loading [2, 12, 20].

Other names

Sodium/phosphate cotransporter 2BNaPi-IIbSolute carrier family 34 member 2NaPi3bNPT2bSLC34A2Type II sodium-dependent phosphate transporter 3b

Antibody-drug conjugate targeting (delivering cytotoxic payloads to overexpressing cells) and inhibition of sodium-dependent phosphate transport (reducing intestinal absorption).