Lumican (LUM) is an extracellular matrix protein with emerging roles in pathological calcification and fibrotic disease progression. As a collagen-binding protein 1, LUM functions in extracellular matrix organization and structural integrity. In calcific aortic valve disease, LUM promotes valve interstitial cell osteogenic transformation through activation of inflammatory pathways and enhanced cellular glycolysis, ultimately driving histone H3 lactylation (H3K14la and H3K9la) at calcification-associated genes including Runx2 and BMP2 1. This represents the first identified role of LUM in histone lactylation-mediated valve calcification. In heart failure, LUM is identified as an oxidative stress-related biomarker with elevated expression primarily in cardiac fibroblasts 2. LUM also functions in pancreatic vascular homeostasis, where LUM+ fibroblasts interact with endothelial cells via multiple ligand-receptor pathways, with disrupted cross-talk observed in diabetes 3. Additionally, LUM was identified as a diagnostic gene in diabetic nephropathy pathogenesis 4. In glioblastoma, LUM expression is transcriptionally regulated by RUNX1 to promote extracellular matrix remodeling and immunosuppressive microenvironment 5. LUM also characterizes fibro-adipogenic progenitor populations enriched in aggressive, chemotherapy-resistant carcinomas 6. These findings position LUM as a promising therapeutic target in multiple fibrotic and calcific diseases.