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Sodium-dependent phosphate transporter 1 (SLC20A1), also known as PiT-1, is a 12-transmembrane protein that functions as a symporter, mediating the uptake of inorganic phosphate into cells using the electrochemical gradient of sodium (UniProt: P17701). It is ubiquitously expressed and plays a vital role in cellular metabolism, signal transduction, and bone mineralization (PubMed: 10852430). SLC20A1 is notably recognized as the primary host cell receptor for the Gibbon Ape Leukemia Virus (GALV) (PubMed: 1643592). The viral envelope glycoprotein (GALV-GP) interacts with the extracellular loops of SLC20A1 to trigger membrane fusion and viral entry. In the context of gene therapy, the R-peptide-deleted version of GALV-GP is frequently used to pseudotype viral vectors because it is constitutively fusogenic, allowing for efficient delivery of genetic material into SLC20A1-expressing target cells (PubMed: 11152503). While SLC20A1 is not a common target for traditional small-molecule drugs, its role in vascular calcification and its overexpression in various cancers make it a subject of therapeutic interest and a key determinant for the tropism of GALV-based biologics (PubMed: 23639503).
The target serves as a docking site for the GALV-GP envelope protein. Binding triggers conformational changes in the GP (especially when the R-peptide is absent) that lead to fusion between the viral envelope and the host cell membrane (PubMed: 11152503). Additionally, it transports inorganic phosphate into the cytoplasm (UniProt: P17701).
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