FBLN1 (fibulin-1) is an extracellular matrix (ECM) glycoprotein with dual roles in structural organization and disease regulation. Located on chromosome 22.2-q13.3, FBLN1 functions as a calcium-binding protein incorporated into fibronectin-containing matrix fibers, facilitating cell adhesion and migration along ECM protein scaffolds 1. The protein regulates multiple signaling pathways, including negative regulation of cell motility and ERK1/2 cascade signaling. FBLN1 acts as a tumor suppressor with established significance in cancer biology. In cutaneous melanoma, FBLN1 expression is frequently silenced through promoter hypermethylation, correlating with tumor progression and reduced overall survival 2. Similarly, melanoma patients with higher FBLN1 expression demonstrate significantly better survival outcomes 3. FBLN1 serves as a biomarker for colorectal cancer, with reduced serum levels distinguishing CRC from benign polyps with 91.8% sensitivity and 100% specificity 4, and emerging evidence supports its role in predicting cetuximab therapy response 5. Beyond oncology, FBLN1 regulates ferroptosis in acute respiratory distress syndrome by inhibiting the TGF-β/Smad pathway, reducing oxidative stress and ferrous iron accumulation 6. In bone biology, circular FBLN1 promotes osteogenic differentiation of mesenchymal stem cells via the let-7i-5p/FZD4 axis and Wnt/β-catenin pathway 7, while FBLN1 enhances chondrocyte proliferation through Smad2 phosphorylation in osteoarthritis 8.