GPC3 (Glypican 3) is a heparin sulfate proteoglycan found on the cell surface of endometrial cells in a number of tissues including the placenta, lung, kidney, breast and adipose tissue. GPC3 forms a complex with and positively regulates Wnt and frizzled proteins to activate downstream signaling cascades, it binds to hedgehog protein SHH and negatively regulates the hedgehog signaling pathway, and it generally functions in the regulation of growth and cell division. Deletions of GPC3 are associated with Simpson-Golabi-Behmel syndrome. In immunohistochemistry, GPC3 has positive staining in the endometrium as well as in high grade hepatitis C. As a tumor marker, GPC3 is used to diagnose hepatocellular carcinoma (HCC), hepatoblastoma, melanoma, testicular germ cell tumors, and Wilms’ tumor. It is a therapeutic target for liver cancers. References: Proteomics. 2007 June. 7 (13): 2300–10. doi:10.1002/pmic.200600654. PMID: 17549790; Hepatology (Baltimore, Md). 2019 Apr, DOI: 10.1002/hep.30646, PMID 30963603; Int J Clin Exp Pathol. 2015; 8(10): 13225–13232, PMID 26722522