Heparanase (HPSE) is an endo-β-glucuronidase whose primary function is to degrade heparan sulfate, a polysaccharide found on cell surfaces and in the matrix. HPSE is expressed in various tissues, particularly overexpressed in tumor cells, and is associated with cell migration, invasion, tumor growth, and metastasis. It facilitates the release and activation of numerous growth factors and cytokines by degrading the extracellular matrix, impacting inflammation, tissue repair, and the tumor microenvironment. The specific expression and mutations of the HPSE gene are related to the progression of various diseases, including cancer and autoimmune diseases. Research into HPSE contributes to the development of new therapeutic strategies, such as inhibitors targeting its activity.