Cell adhesion, proliferation, differentiation and migration depend on the interaction of extracellular ligands with cell surface receptors. In many instances, the ligand initially binds to cell surface heparan sulfate proteoglycans (HSPGs), which may concentrate the ligand or change its conformation, thereby enhancing the interaction of the ligand with its protein receptor. One way to regulate the HSPG co-receptors is to degrade the heparan sulfate (HS) glycosaminoglycans. This is accomplished by intracellular heparanases which, once the cell surface HSPGs have been internalized, cleave the HS chains from the proteoglycan core protein and degrade them to short glycosaminoglycans. The short HS chains created by heparanases may protect ligands in endosomes or transport them to other sites of actions within the cell. The long-term goals of my research are to determine the number of intracellular heparanases and characterize their molecular and enzymatic properties to understand how they create the short HS chains found inside cells. We have purified a novel intracellular heparanase from Chinese hamster ovary cells, however protein sequencing suggests that it is proteolytically derived from the ERM proteins that function in cell morphology and adhesion. We are using physical and molecular biological techniques to determine whether our purified heparanase is indeed derived from the ERM proteins.