CILP (cartilage intermediate layer protein) is a secreted extracellular matrix glycoprotein encoded by a single-copy gene on chromosome 15, organized in nine exons spanning approximately 15.3 kbp 1. The protein functions primarily as a negative regulator of growth factor signaling in cartilage. CILP antagonizes transforming growth factor-beta1 (TGF-β1) and insulin-like growth factor-1 (IGF-1) signaling by suppressing IGF-1-induced chondrocyte proliferation and inhibiting IGF1 receptor autophosphorylation, while also modulating SMAD protein signal transduction 2. Additionally, CILP mediates ferroptosis-related gene regulation through the miR-140-3p/CILP axis, affecting oxidative stress and inflammatory responses 3. In osteoarthritis, CILP+ synovial fibroblasts exert protective effects on chondrocytes through cell proliferation promotion and inflammation inhibition, contrasting with pro-degenerative POSTN+ fibroblasts 2. CILP expression correlates with osteoarthritis progression severity and serves as a potential disease marker 4. Regarding lumbar disc disease, genetic associations vary by population: the CILP rs2073711 GG genotype shows reduced disease risk in Indian populations 5, while the +1184T→C SNP shows ethnicity-dependent associations 6. Beyond musculoskeletal tissues, CILP marks persistently activated cardiac fibroblasts in heart failure and demonstrates pan-cancer significance as a potential prognostic marker 78.