SULF1 (sulfatase 1) is a heparan sulfate-modifying enzyme that removes 6-O-sulfate groups from glucosamine residues within heparan sulfate proteoglycans (HSPGs) 1. By desulfating HSPGs, SULF1 alters their co-receptor function and modulates signaling by heparin-dependent growth factors including FGF, VEGF, and HGF 2. This enzymatic activity has context-dependent pathological consequences: in fibrotic diseases, SULF1 promotes fibroblast activation and collagen deposition through TGF-β1/SMAD pathway activation 34. In cancer, SULF1-expressing cancer-associated fibroblasts enhance VEGFA bioavailability and support tumor angiogenesis and progression 5. SULF1 is also implicated in atherosclerosis and endothelial senescence 67. Notably, SULF1 expression is elevated in idiopathic pulmonary fibrosis (IPF), cardiac fibrosis, and colorectal cancer 348, and its expression is suppressible by histone deacetylase inhibitors through microbiota-derived butyrate signaling 5. These findings position SULF1 as a pro-fibrotic and pro-tumoral effector with therapeutic potential as a disease biomarker and treatment target.