Sodium-dependent phosphate transport protein 2B (NaPi2b) (NaPi2b)

Sodium-dependent phosphate transport protein 2B (NaPi2b), encoded by the SLC34A2 gene, is a multi-pass transmembrane protein that mediates the active transport of inorganic phosphate into cells alongside sodium ions (UniProt: P78367). It plays a vital role in maintaining systemic phosphate homeostasis and is primarily expressed in the brush border membrane of the small intestine for dietary absorption, as well as in the lungs and salivary glands (PubMed: 22336971). In oncology, NaPi2b is highly overexpressed in several solid tumors, most notably epithelial ovarian cancer and non-small cell lung cancer adenocarcinoma, while maintaining limited expression in normal vital tissues (PubMed: 32661010). This differential expression profile makes it an attractive target for therapeutic intervention, particularly through antibody-drug conjugates (ADCs) designed to deliver potent cytotoxics directly to tumor cells. Conversely, loss-of-function mutations in the SLC34A2 gene are the primary cause of pulmonary alveolar microlithiasis, a rare condition where calcium phosphate deposits accumulate in the lungs (PubMed: 16473914). Clinical development of NaPi2b-targeted therapies has faced challenges, including managing on-target off-tumor toxicities such as pneumonitis and interstitial lung disease (ClinicalTrials.gov: NCT03319628).

Other names

SLC34A2Sodium/phosphate cotransporter 2BNaPi-IIbNAPI-3BSolute carrier family 34 member 2

Targeted delivery of cytotoxic agents via antibody-drug conjugates (ADCs) binding to the extracellular domain of NaPi2b; inhibition of sodium-dependent phosphate transport.