SLC20A2 encodes a sodium-phosphate cotransporter (PiT2) that plays critical roles in brain phosphate homeostasis and neuronal function. The protein is highly expressed in astrocytes where it exhibits polarized distribution throughout astrocyte processes, functioning as a phosphate importer that is essential for maintaining brain phosphate balance 1. Beyond phosphate transport, SLC20A2 regulates hippocampal-dependent learning and memory by promoting neuronal branching and survival, independently of its phosphate transport ability 2. Loss-of-function mutations in SLC20A2 cause primary familial brain calcification (PFBC), an autosomal dominant disorder characterized by bilateral calcium-hydroxyapatite crystal deposition in basal ganglia and other brain regions 3. The pathogenesis involves disrupted phosphate homeostasis, impaired endothelial function, and compromised blood-brain barrier integrity 3. Clinically, PFBC presents with movement disorders, cognitive deficits, and psychiatric disturbances, though nearly one-third of cases remain asymptomatic despite brain calcification 4. Novel therapeutic approaches include antisense oligonucleotides that can restore SLC20A2 expression and reduce brain calcification in mouse models 5. The protein also functions as a retroviral receptor, conferring susceptibility to certain murine and feline leukemia viruses, highlighting its diverse biological roles.