HPSE2

HPSE2, also known as heparanase-2 or Hpa2, is a human gene that encodes a protein related to the heparanase family. Like its family member HPSE1, HPSE2 shares sequence similarity with enzymes that interact with heparan sulfate; however, HPSE2 is generally considered catalytically inactive or to have markedly reduced endo-β-D-glucuronidase activity, due in part to differences in its catalytic region. Despite limited enzymatic activity, HPSE2 can bind to heparan sulfate proteoglycans and is thought to influence extracellular matrix remodeling and signaling events.

Functionally, HPSE2 is often described as a regulator of heparan sulfate turnover. It may act as a decoy receptor or endogenous inhibitor of HPSE1 by competing for substrate or forming inactive complexes, thereby modulating the overall degradation of the extracellular matrix. This regulatory role has generated interest in contexts such as cancer biology, angiogenesis, and inflammatory processes, where HPSE1 activity promotes basement membrane degradation and release of growth factors.

Expression studies have detected HPSE2 in multiple tissues, and the protein is found associated with cellular membranes and extracellular compartments in various contexts. The precise physiological roles and regulatory mechanisms of HPSE2 remain under investigation, with research spanning cell culture systems, animal models, and human tissues.

Clinical and research relevance is ongoing but not definitive. Deregulation of HPSE2 has been investigated in relation to tumor progression and treatment response in some cancers, though findings are not yet conclusive, and HPSE2 is not a standard clinical biomarker. HPSE2 is conserved across vertebrates, and its genomic organization and regulation continue to be active areas of study.