Hepatoma derived growth factor (HDGF) is the original member of a family of polypeptides designated HDGF-related proteins (HRPs). HDGF was initially characterized as a secreted mitogen from the Huh-7 human hepatoma cell line. This nuclear targeted vascular smooth muscle cell mitogen (VSM) is a heparin-binding protein that is highly expressed in tumor cells, where it stimulates proliferation. HDGF is also reported to be involved in organ development and lung remodeling after injury by promoting proliferation of lung epithelial cells. During development, HDGF expression is high in the nucleus and cytoplasm of smooth muscle and endothelial cells. The HRP family contains four proteins, HRP-1, HRP-2, HRP-3 and HRP-4. HRP-1 and HRP-4 are expressed only in testis, while HRP-2 is widely expressed in different tissues. HRP-3 can be found solely in the nervous system. Specifically it is strongly expressed in bulbus, olfactorius, piriform cotrex and amygdala complex, while HRP-2 in brain is located in the the thalamus, prefrontal and parietal cortex, neurohypophysis and cerebellum. In the central nervous system, HRPs play a role in neuron proliferation and cell survival.