DSE (dermatan sulfate epimerase) functions as a C5 epimerase that converts D-glucuronic acid to L-iduronic acid residues in chondroitin sulfate chains, playing a crucial role in dermatan sulfate biosynthesis 1. The enzyme catalyzes the formation of chondroitin sulfate/dermatan sulfate (CS/DS) hybrid chains and directly mediates DS chain formation in cells 2. DSE expression shows significant clinical relevance in cancer biology, where it is upregulated in gliomas and associated with advanced tumor grade and poor survival 2. In glioblastoma, DSE promotes aggressive cellular phenotypes including proliferation, migration, and invasion by selectively regulating heparin-binding EGF-like growth factor (HB-EGF)-induced signaling through the ErbB pathway 2. Conversely, in melanoma, DSE is downregulated in tumor tissues, and high DSE expression inhibits tumor progression by promoting immune cell infiltration and regulating VCAN expression 1. DSE is also associated with musculocontractural Ehlers-Danlos syndrome, where pathogenic variants cause a milder phenotype compared to CHST14 mutations, characterized by craniofacial features, joint contractures, and connective tissue fragility without major cardiovascular or respiratory complications 3. The tissue-specific and context-dependent roles of DSE highlight its importance in both normal development and disease pathogenesis.