PiT2

PiT2, or phosphate transporter 2, is a mammalian protein that functions as a sodium-dependent transporter of inorganic phosphate (Pi). It is encoded by the SLC20A2 gene in humans and belongs to the PiT family, which also includes PiT1 (SLC20A1). These proteins are classified as type III sodium-phosphate cotransporters and participate in cellular Pi uptake.

PiT2 is broadly expressed in many tissues, with notable expression in the brain and kidney. It mediates the import of phosphate into cells by coupling Pi transport to the sodium gradient across the plasma membrane. In the brain, PiT2 is thought to contribute to local phosphate homeostasis, while in the kidney it may participate in phosphate handling along the nephron. The transporter can move phosphate in symport with sodium and may also transport related substrates such as arsenate in some contexts.

Structurally, PiT2 is predicted to contain multiple transmembrane helices with both N- and C- termini facing the cytoplasm, and extracellular loops that are glycosylated. Transport activity depends on sodium concentration, membrane potential, and possibly regulatory interactions with other proteins.

Clinical significance: Mutations in SLC20A2 have been linked to idiopathic basal ganglia calcification (IBGC), also known as Fahr disease. The disorder is characterized by calcifications in the basal ganglia and other brain regions and can present with movement disorders, cognitive changes, or neuropsychiatric symptoms. The condition is typically inherited in an autosomal dominant pattern with variable penetrance. Other IBGC-associated genes include PDGFB and PDGFRB.

See also: SLC20A1 (PiT1); idiopathic basal ganglia calcification; phosphate transport.