Studies employing model systems from cell and tissue culture to zebrafish have determined critical role(s) for heparan sulfate chains of proteoglycans in vascular development and regeneration. Heparan sulfate chain interactions with growth factors and their receptors have been proposed to explain these requirements. Recently, our studies have confirmed the identification of a membrane protein (TMEM184A) that acts as a receptor for heparin (and heparan sulfate, by extension). This receptor plays a role in signal transduction and heparin uptake in cultured vascular cells. To examine the role of this receptor in a vertebrate organism, we employed zebrafish, and the specific TG(fli1-EGFP) transgenic line to evaluate the presence of the receptor and its function in angiogenesis. We have identified this protein (TMEM184A) in ontogenic and regenerating zebrafish vasculature through co-immunofluorescence with GFP in Tg(fl1-EGFP) zebrafish. The heparin receptor co-localizes with GFP in both arteries and veins in ontogenic tail fin rays from the fish. After amputation to approximately 50%, immunofluorescence confirms localization of the heparin receptor matching the GFP pattern in regenerates. In tissue culture systems, cell proliferation is increased in cells where TMEM184A is knocked down. Knock-down fin rays have larger numbers of GFP containing vascular cells, and the cells are more disorganized than either untreated or control morpholino treated fins. This effect is reversible. Transient knockdown using morpholinos results in significantly less TMEM184A staining in regenerating vessel cells within 24 hours of morpholino injection. These studies indicate expression of the heparin receptor in zebrafish endothelial cells and a modulatory role in angiogenesis. Coupled with information from cultured cells where heparin treatment decreases cell proliferation and receptor knockdown allows more extensive proliferation, these studies suggest that heparan sulfate chains from proteoglycans interact with the heparin receptor in this modulatory function.