PRELP (proline and arginine rich end leucine rich repeat protein) is a small leucine-rich proteoglycan that functions as an extracellular matrix component with diverse roles in tissue homeostasis and disease. The protein binds type I collagen to basement membranes and type II collagen to cartilage, potentially anchoring basement membranes to underlying connective tissue 1. PRELP operates through multiple receptor interactions, including binding to p75NTR to activate FAK/MAPK signaling pathways in adipocytes 2 and to integrin α5 to modulate cell stiffness and adhesion 3. Mechanistically, PRELP functions as a natural TGF-β antagonist, effectively attenuating fibroblast response to TGF-β1 stimulus and reducing cell contractile capacity 4. The protein also binds FGF1, reducing its stability and inactivating the PI3K/AKT/mTOR pathway 5. PRELP shows context-dependent disease relevance, being upregulated in obesity and associated with metabolic disorders 2, while demonstrating tumor-suppressive effects in colorectal cancer by inhibiting epithelial-mesenchymal transition and angiogenesis 5. In osteoarthritis, PRELP expression in specific synovial fibroblast populations correlates with protective effects on chondrocytes 6. The gene lacks a TATA box and is regulated by Sp1-binding sites, with expression appearing after the third month of birth 71.