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 to the EGF receptor with a higher affinity and has been shown to bemore mitogenic, likely due to its ability to bind to heparin and heparin sulfate proteoglycans. HB-EGF has also been reported to act as a diphtheria toxin receptor, mediating endocytosis of the bound toxin. Heparin-binding EGF-like growth factor has been shown to interact with NRD1, Zinc finger and BTB domain-containing protein 16 and BAG1.