SLC20A1 (PiT1) is a sodium-dependent inorganic phosphate cotransporter with dual roles in phosphate homeostasis and cellular signaling. As a primary function, SLC20A1 mediates phosphate uptake across the plasma membrane 1 and is dynamically regulated by phosphate availability, with protein expression induced during phosphate starvation through post-transcriptional mechanisms involving ESCRT-mediated degradation under phosphate-replete conditions 1. Beyond phosphate transport, SLC20A1 functions as a retroviral receptor for Gibbon Ape Leukemia Virus and other retroviruses, and serves as the cellular receptor for syncytin-B, an endogenous retroviral envelope protein essential for mouse placental syncytiotrophoblast formation 2. In the nervous system, SLC20A1 independently promotes synaptic plasticity and cognition through mechanisms distinct from phosphate transport, likely involving Otoferlin-dependent regulation of GABAergic synaptic vesicle trafficking 3. Disease relevance includes associations with combined pituitary hormone deficiency and cognitive disorders 4, while computational studies identify missense variants (C573F, T58A) as deleterious 4. Clinically, SLC20A1 overexpression correlates with poor prognosis in head and neck squamous cell carcinoma, predicting aggressive cellular behaviors and chemotherapy response 5. Additionally, SLC20A1 serves as a validated diagnostic biomarker for preeclampsia 6 and mediates intestinal Lactobacillus attachment affecting oncolytic virotherapy efficacy 7.