Heparanase 2 (HPSE2)

Heparanase 2 (HPSE2) is a structural homolog of heparanase 1 but lacks any endoglycosidase enzymatic activity. Instead, it binds heparan sulfate with high affinity and is thought to competitively inhibit heparanase 1, influencing cell migration, matrix remodeling, and growth factor signaling. HPSE2 is involved in development of the nervous system, maintaining vascular and endothelial integrity, and protecting against tissue injury in inflammatory and diabetic kidney disease. In cancer, HPSE2 is frequently downregulated, suggesting a tumor-suppressor role. Loss-of-function mutations in HPSE2 cause urofacial syndrome, characterized by abnormal urinary tract and facial development. Therapeutic interest centers around mimicking or increasing HPSE2 function to antagonize heparanase 1 activity, but there are currently no approved drugs targeting HPSE2[1][3][4][5].

Other names

Inactive heparanase-2HPA2Hpa2HPR2UFSUFS1heparanase 3heparanase-like protein

Competitive inhibition of heparanase 1 activity by high-affinity HS binding Protection of cellular and vascular structures against inflammatory injury (through inhibition of HS shedding)