Collectively, the heparan sulfate–heparanase axis plays pivotal roles in creating a permissive environment for cell proliferation, differentiation, and function, often resulting in the pathogenesis of diseases, such as cancer, chronic inflammation, sepsis, endotheliitis, kidney dysfunction, diabetic nephropathy, diabetes, tissue fibrosis, bone osteolysis, thrombosis, atherosclerosis, and viral infection [36]. Here, HPSE is linked to cancer.