Solute carrier family 15 (SLC15) (SLC15)

The Human Solute carrier family 15 (SLC15) consists of proton-coupled oligopeptide transporters, primarily PEPT1 (SLC15A1) and PEPT2 (SLC15A2), which play a critical role in the uptake and reabsorption of di- and tripeptides (UniProt P46059, Q16348). These transporters are highly significant in pharmacology because they recognize and transport a wide variety of peptidomimetic drugs, including beta-lactam antibiotics, ACE inhibitors, and antiviral prodrugs like valacyclovir (PMID: 23506880). PEPT1 is predominantly expressed in the apical membrane of intestinal epithelia, facilitating the absorption of dietary proteins and oral medications, while PEPT2 is found in the kidney, lung, and choroid plexus, contributing to renal reabsorption and neuropeptide homeostasis (PMID: 33035570). Beyond nutrient and drug transport, family members like SLC15A3 and SLC15A4 are involved in innate immune signaling by transporting bacterial breakdown products to intracellular receptors (PMID: 25624444). Dysregulation of SLC15 transporters is associated with conditions such as inflammatory bowel disease and certain cancers, where they may be exploited for targeted drug delivery (PMID: 21084631). Understanding the substrate specificity and expression patterns of the SLC15 family is essential for optimizing the pharmacokinetic profiles of peptide-like therapeutic agents.

Other names

Proton-coupled oligopeptide transportersPOT familyPeptide transportersPEPT familyH+/peptide cotransporters

Proton-coupled secondary active transport (symport) of di- and tripeptides and peptidomimetic drugs across cell membranes.