SLC15A3 is a proton-coupled endolysosomal peptide transporter that mediates the transport of free histidine, di- and tripeptides, and carnosine across lysosomal membranes 1. It preferentially binds short peptides with basic residues at the first position and hydrophobic residues at the second position 1. Functionally, SLC15A3 plays a critical role in innate immune responses by facilitating transport of bacterial peptidoglycans, such as muramyl dipeptide, which activates NOD-like receptor signaling 2. The transporter is upregulated by Toll-like receptor ligands via NF-κB and MAPK signaling 2 and enhances interferon production through interactions with MAVS and STING in antiviral responses 3. SLC15A3 also recruits the adapter protein TASL for IRF5 activation downstream of endolysosomal TLR signaling 1. Pathologically, SLC15A3 upregulation contributes to idiopathic pulmonary fibrosis through oxidative stress in alveolar macrophages via the p62-NRF2 antioxidant pathway 4. Additionally, m6A-mediated upregulation of SLC15A3 drives M1 macrophage polarization in psoriasis through enhanced TASL-IRF5 signaling 5. SLC15A3 also serves as a prognostic biomarker in cervical cancer, associated with circadian rhythm dysregulation 6. Targeting SLC15A3 represents a therapeutic approach for fibrotic and inflammatory diseases 7.