Inorganic phosphate (Pi) levels are hormonally regulated that affects the physiological activity of bone, kidney, and small intestine. Majority of the Pi is absorbed in the small intestine and reabsorbed in the proximal tubules in the kidney. At least 4 groups of structurally and functionally related proteins are in involved in Pi transport: Type I-related NaPi transporters designated NPT1, Npt1, and NaPi-1 respectively in humans, mouse, and rabbit are expressed in the kidney and liver. Its expression and activity are not regulated by Pi deprivation or parathyroid hormone (PTH) and its role in Pi-homeostasis is not clear. Type IIa-related cotransporters, designated NaPi-2 in rat, NaPi-3 or NPT2 in humans, NaPi-4 in opossum, NaPi-5 in flounder vessel, NaPi-6 or Npt-2 in mouse, and NaPi-7 in rabbit, is the primary target for Pi regulation by dietary, hormonal, and tubular Pi reabsorption. Deletion of Npt2 gene produces severe Pi wasting. Type II transporters are expressed in kidney, brain, lung, bone and small intestine. Type IIb, designated as NaPi-IIB or NaPi-2b in rat/mouse, and NaPi-3b in human, is closely related isoform of the NaPi-2 family. It is expressed in small intestine and lung. Type III NaPi transporters, originally described as a family of cell surface receptors for gibbon ape leukemia virus (GALV) and murine amphotropic retrovirus (A-MuLv), share very low (<20%) sequence homology with Type I and II proteins, and are found in most tissues. Human homolog is now designated as PiT1 (also known as GALV receptors or GLVR1) and PiT2 (A-MuLV receptors or GLVR2 or Ram1). Pit1 and Pit2 are ~62% related and predicted to contain 10 TM domains that is in contrast with Type 1/2 transporters (6-8 TM). The N and C-termini are predicted to be cytoplasmic.