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

Sodium-dependent phosphate transport protein 2B (NaPi-IIb), encoded by the SLC34A2 gene, is a multi-pass membrane protein that plays a critical role in maintaining phosphate homeostasis by mediating the transport of inorganic phosphate into epithelial cells [UniProt: O95436]. It is primarily expressed in the brush border membrane of the small intestine, where it is responsible for the majority of active intestinal phosphate absorption [PubMed: 24651937]. The transporter is also found in the apical membrane of type II pneumocytes in the lungs, where it helps clear phosphate from the alveolar space to prevent the formation of calcium phosphate crystals [PubMed: 24651937]. In the context of chronic kidney disease (CKD), NaPi-IIb is a therapeutic target for managing hyperphosphatemia, as its inhibition can reduce the systemic absorption of dietary phosphate [PubMed: 30135104]. Furthermore, NaPi-IIb is significantly overexpressed in certain malignancies, including ovarian cancer and non-small cell lung cancer, which has led to its development as a target for antibody-drug conjugates (ADCs) [PubMed: 32855157]. These ADCs, such as upifitamab rilsodotin, utilize the high expression of NaPi-IIb to deliver potent cytotoxic agents directly to tumor cells while minimizing systemic toxicity [PubMed: 32855157]. However, targeting NaPi-IIb presents challenges, particularly regarding potential pulmonary toxicity due to its physiological role in the lung [PubMed: 29453245]. Clinical trials for small molecule inhibitors have also explored their use as adjuncts to traditional phosphate binders to improve control of serum phosphorus levels in dialysis patients [PubMed: 30135104].

Other names

SLC34A2Sodium/phosphate cotransporter 2BNa(+)/Pi cotransporter 2BSolute carrier family 34 member 2

Inhibition of sodium-dependent phosphate cotransport to reduce systemic phosphate levels; Targeted delivery of cytotoxic agents via antibody-drug conjugates in oncology.