Proheparin-binding EGF-like growth factor (HB-EGF), also known as DTR, DTS and HEGFL, is a member of the EGF family of mitogens. It is expressed in macrophages, monocytes, endothelial cells and muscle cells. HB-EGF signals through the EGF receptor to stimulate the proliferation of smooth muscle cells, epithelial cells and keratinocytes. Compared to EGF, HB-EGF binds the EGF receptor with higher affinity and is thus more mitogenic, probably due to its ability to bind to heparin and heparin sulfate proteoglycans. HB-EGF has been reported to act as a diphtheria toxin receptor, mediating endocytosis of the bound toxin.