Solute carrier family 15 member 1 and 2 (SLC15A1 and SLC15A2) (SLC15A1/SLC15A2)

Solute carrier family 15 member 1 (SLC15A1, also known as PEPT1) and member 2 (SLC15A2, or PEPT2) are integral membrane proteins belonging to the proton-coupled oligopeptide transporter (POT) family. SLC15A1 is primarily expressed on the apical membrane of enterocytes in the small intestine, where it is responsible for the high-capacity, low-affinity absorption of dietary di- and tripeptides (UniProt P46059). In contrast, SLC15A2 is a high-affinity, low-capacity transporter predominantly found in the kidney's proximal tubules, the choroid plexus of the brain, and the lungs, where it facilitates the reabsorption and conservation of peptides (UniProt Q16348). These transporters are of significant pharmacological interest because they recognize and transport a broad range of peptidomimetic drugs, including beta-lactam antibiotics, ACE inhibitors, and antiviral prodrugs like valacyclovir, thereby determining their oral bioavailability and tissue distribution (Smith et al., 2013, Molecular Aspects of Medicine). In pathological conditions, SLC15A1 is notably upregulated in the colon during chronic inflammation, such as in Crohn's disease and ulcerative colitis, where it may transport bacterial peptides that further stimulate inflammatory responses (Ingersoll et al., 2012, Experimental Biology and Medicine). Consequently, SLC15A1 and SLC15A2 are critical targets for drug design strategies aimed at improving the delivery of poorly absorbed therapeutic agents.

Other names

PEPT1PEPT2Peptide transporter 1Peptide transporter 2H+/peptide cotransporter 1H+/peptide cotransporter 2Oligopeptide transporter 1Oligopeptide transporter 2

These transporters function as proton-coupled symporters that utilize an inwardly directed electrochemical proton gradient to drive the transmembrane movement of di- and tripeptides, as well as various peptidomimetic drugs, into the cytoplasm.