XPR1 (xenotropic and polytropic retrovirus receptor 1) functions as the sole inorganic phosphate (Pi) exporter in human cells, playing a critical role in cellular phosphate homeostasis 1. The protein operates as an inositol phosphate-activated phosphate channel, mediating phosphate efflux across the plasma membrane to prevent toxic intracellular phosphate accumulation 23. XPR1 activity is regulated through binding of inositol pyrophosphates, particularly inositol hexakisphosphate (InsP6) and 1,5-InsP8, which bind to the SPX domain and trigger conformational changes that open the transport pathway 23. The protein requires KIDINS220 as a partner for proper cellular localization and activity, forming a complex that undergoes synergistic activation 14. In astrocytes, XPR1 shows polarized distribution at blood vessel end-feet, contributing to brain phosphate homeostasis 5. Disease-wise, XPR1 mutations cause primary familial brain calcification (PFBC, also known as Fahr's disease), an autosomal dominant disorder characterized by bilateral basal ganglia calcifications and neurological symptoms including movement disorders, cognitive decline, and psychiatric manifestations 67. Additionally, XPR1 dysregulation represents a therapeutic vulnerability in ovarian cancer, where disruption of the XPR1-KIDINS220 complex leads to toxic phosphate accumulation and cell death 1.