Proheparin-binding EGF-like growth factor (HB-EGF), also known as DTR, DTS and HEGFL, is a 13-15kDa 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 be more mitogenic, likely due to its ability to bind to heparin and heparin sulfate proteoglycans. It has been shown to play a role in wound healing, cardiac hypertrophy and heart development and function. The transmembrane form of HB-EGF is the unique receptor for diptheria toxin and functions in juxtacrine signaling in cells. Both forms of HB-EGF participate in normal physiological processes and in pathological processes including tumor progression and metastasis, organ hyperplasia, and atherosclerotic disease. HB-EGF can bind two locations on cell surfaces, heparan sulfate proteoglycans and EGF-receptor effecting cell to cell interactions.