SLC15A1 (PepT1) is an electrogenic proton-coupled amino acid transporter that functions as the primary intestinal absorber of dietary di- and tripeptides, with preference for dipeptides 1. The transporter operates via H+-coupled symport with a proton-to-peptide stoichiometry of 1:1 or 2:1, mediating transepithelial transport of neutral and monovalently charged peptides 1. Beyond nutrient absorption, SLC15A1 recognizes pathogenic bacterial peptides including muramyl and N-formylated dipeptides, contributing to mucosal immune surveillance 1. Therapeutically, SLC15A1 significantly influences drug bioavailability, facilitating oral absorption of beta-lactam antibiotics, ACE inhibitors, and nucleoside antivirals through direct transport or prodrug strategies; valaciclovir exemplifies enhanced acyclovir bioavailability via valine esterification and subsequent SLC15A1-mediated absorption 2. However, some cyclic peptide drugs like octreotide are nonsubstrate inhibitors rather than transportable substrates 3. SLC15A1 exhibits pronounced molecular diversity across species, including pH and temperature adaptations in teleost models 4. Genetically, SLC15A1 variants associate with bladder cancer susceptibility in Chinese populations; the rs4646227 polymorphism showed significant association with increased cancer risk 5. Mutation screening in bipolar disorder families identified only polymorphic variants without causative mutations 6. SLC15A1 expression is highest in jejunum among major tissues 7, establishing it as critical for both nutrient homeostasis and pharmaceutical absorption.