Heparin-binding epidermal growth factor (HB-EGF), like BTC, is a heparin-binding EGF family member. Natural soluble HB-EGF is a 19 kDa glycoprotein of multiple forms due to heterogeneous truncations. Soluble HB-EGF is mitogenic and chemotactic for fibroblasts, keratinocytes, and smooth muscle cells but not capillary endothelial cells. Production of HB-EGF is detected in monocytes, macrophages, and vascular and aortic smooth muscle cells (SMC). HB-EGF may play a role in the pathogenesis of atherosclerosis. It may also be an effector of Jun-induced oncogenic transformation. HB-EGF binds to EGFR with high affinity and to ErbB with moderate affinity.