Preclinical data suggest that during sepsis, syndecan-1 ectodomains can be cleaved from the endothelial cell membrane by matrix metalloproteinases (MMPs).39-42 The precise interplay between heparanase-mediated HS disaccharide fragmentation and MMP-mediated syndecan-1 cleavage is evolving, with evidence demonstrating that heparanase plays a role in enhancing syndecan-1 shedding by upregulating MMP expression.43 The gene discussed is HPSE; the disease is Sepsis.