Solute carrier family 15 member 2 (SLC15A2), also called peptide transporter 2 (PepT2), is a member of the proton-coupled oligopeptide transporter (POT) family of integral membrane proteins that mediate the cellular uptake of di/tripeptides and peptide-like drugs. The POT family belongs to the Major Facilitator Superfamily (MFS) of membrane transport proteins. SLC15A2, as well as SLC15A1, mediate the proton-coupled active transport of a broad range of dipeptides and tripeptides, including zwitterionic, anionic and cationic peptides, as well as a variety of peptide-like drugs such as cefadroxil, enalapril, and valacyclovir []. SLC15A2 is a high-affinity transporter and is abundantly expressed in the apical membrane of kidney proximal tubules and choroid plexus epithelial cells. It is the major transporter involved in the reclamation of peptide-bound amino acids and peptide-like drugs in the kidney, and is also called the renal isoform. In choroid plexus and the brain, it acts as an efflux transporter and plays a role in regulating peptide/neuropeptide homeostasis []. SLC15A2, as a member of MFS, is thought to function through a single substrate binding site, alternating-access mechanism involving a rocker-switch type of movement.
