Syndecan-4 is a transmembrane (type I) heparan sulfate proteoglycan that functions as a receptor in intracellular signaling. The protein is found as a homodimer and is a member of the syndecan proteoglycan family. Syndecan-4 interacts with extracellular matrix, anticoagulants, and growth-factors. It also regulates the actin cytoskeleton, cell adhesion, and cell migration. Syndecan-4 activates protein kinase C (PKC), an enzyme involved in signal transduction. The variable domain of syndecan-4 could be a site of self-association. The degree of oligomerization correlates with the activity of kinases, so the degree of clustering of syndecan-4 correlates to PKC activity. Syndecan-4 also binds to phosphatidylinositol (4,5)-bisphosphate (PIP2) through the variable domain and increases PKC activity ten-fold. Syndecan-4 is also a regulator of fibroblast growth factor-2 (FGF-2) signaling. Syndecan-4 binds to FGF and mediates interaction with the FGF receptor. Because the tight correlation between syndecan-4 and growth factors, the efficiency of angiogenic therapies have been thought to relate to syndecan-4. Growth factor signaling may be disrupted by changes in syndecan-4 expression. The cellular uptake, trafficking, and nuclear localization of FGF-2 could be increased by co-delivery of syndecan-4 proteoliposomes. These alterations should be considered in FGF-2-based therapies. Syndecan-4 is also associated with the healing process. Lack of Sdc4 gene causes delayed wound healing in mice. This delay may be due to compromised fibroblast motility.