GLCE (D-glucuronyl C5-epimerase) is a key enzyme in heparan sulfate biosynthesis that converts D-glucuronic acid residues to L-iduronic acid residues in maturing heparan sulfate and heparin chains 1. The enzyme functions as a homodimer and catalyzes critical modifications that determine glycosaminoglycan-protein interactions 1. Beyond its enzymatic role, GLCE exhibits diverse cellular functions including serving as a cell-surface factor that facilitates viral entry, as demonstrated with porcine deltacoronavirus where GLCE promotes viral attachment and internalization by interacting with spike proteins 2. In kidney pathophysiology, GLCE acts as an anti-fibrotic factor independent of its enzymatic activity by binding to EGFR and suppressing EGFR/ERK and TGF-β/Smad signaling pathways 3. The gene shows complex tumor-context-dependent roles: it functions as a tumor suppressor in breast cancer with expression regulated by TCF4/β-catenin pathways and chr15 modifications 4, while in prostate cancer, increased GLCE expression correlates with advanced disease and promotes angiogenesis in a cell-type-specific manner 56. GLCE expression is also enhanced by butyrate treatment in mast cells, increasing heparin synthesis and storage 7. These findings reveal GLCE as a multifunctional protein with both metabolic and signaling roles across various pathological contexts.