L-Proline occupies a unique position among the 20 proteinogenic amino acids. Two of the most recently cloned members of the solute carrier family are "proline transporters": The amino acid transporter PAT1, mainly expressed in intestine and brain transports L- and D-proline, GABA and others in a pH gradient dependent manner. In 2005 the Na⁺/imino acid transporter SIT1 was cloned. For studies of the peptide transporter PEPT1, expressed at the apical membrane of intestinal, renal and biliary duct epithelial cells, L-proline containing peptides are of particular interest because (1) Xaa-Pro peptides are very often resistant to enzymatic hydrolysis and display a high affinity to PEPT1, (2) the decisive factor for their transport is a trans peptide bond conformation, (3) many biologically important peptide sequences contain highly conserved proline residues, (4) several orally available angiotensin converting enzyme inhibitors are Xaa-Pro derivatives recognized by PEPT1 because of their sterical resemblance to small peptides and (5) side chain modification of Xaa-Pro dipeptides led to the development of the first non-transported, high-affinity inhibitors of PEPT1 and PEPT2.

Future studies will demonstrate the proportional contribution of PAT1, SIT1, PEPT1/2 and others in epithelial imino acid transport.