FBLN5 (fibulin-5) is an extracellular matrix protein essential for elastic fiber assembly and vascular function. Primary function: FBLN5 mediates elastin polymer assembly and microfibrillary organization in skin, lung, and vasculature through interactions with elastin and fibrillin-1 1. It promotes endothelial cell adhesion via integrin-RGD motif interactions and serves as a vascular ligand for integrin receptors 2. Mechanism: FBLN5 expression is regulated by TGF-β signaling through Smad-dependent and PI3-kinase/Akt pathways in lung fibroblasts 3. Post-translational citrullination by PAD2 protects FBLN5 from proteolysis, enhancing its elastogenic activity 4. Disease relevance: FBLN5 mutations cause autosomal dominant and recessive cutis laxa, Charcot-Marie-Tooth disease type 1H, and age-related macular degeneration 5. Fbln5 knockout mice show accelerated arterial stiffening equivalent to advanced aging 6. Clinical significance: Reduced FBLN5 expression in pelvic organ prolapse impairs collagen synthesis through the FOSL1/miR-222/MEIS1 axis 7. In non-small-cell lung cancer, CAF-derived FBLN5 promotes radioresistance via integrin αVβ5-Src-STAT3 signaling and ferroptosis inhibition, serving as a biomarker for radiotherapy response 8.