Oligopeptide Cotransporter

Oligopeptide cotransporters are a class of membrane transport proteins that rely on the proton gradient (H+ gradient) and belong to the SLC15 proton-coupled transporter family. They are primarily responsible for the transmembrane transport of oligopeptides (small peptides composed of 2-4 amino acid residues) and their analogs (such as β-lactam antibiotics, antiviral drugs, etc.).
Oligopeptide cotransporter family includes four members: SLC15A1-SLC15A4. SLC15A1 (also known as PEPT1) is a low-affinity, high-capacity transporter mainly distributed on the brush border membrane of small intestinal epithelial cells, mediating the absorption of dietary oligopeptides and the intestinal uptake of drugs. In contrast, SLC15A2 (PEPT2) is a high-affinity, low-capacity transporter highly expressed in the proximal tubules of the kidney and the central nervous system (choroid plexus, astrocytes), participating in the renal tubular reabsorption of oligopeptides and the distribution of drugs in the brain. SLC15A3 (PHT2) and SLC15A4 (PHT1) are localized to the lysosomal membrane, primarily transporting small peptides and histamine, and regulating lysosomal function and TLR signaling pathway activation in immune cells (such as dendritic cells, B cells), which are closely related to autoimmune diseases (such as systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD)).
Oligopeptide cotransporters play crucial roles in various physiological processes, including drug absorption and immune responses^[1][2][3][4.