Overexpression of RasGRP3 in glioma cells that express low levels of this protein increased both Ras and Rap1 activity whereas silencing of endogenous RasGRP3 expression in glioma cells that express high levels of this protein decreased Ras but not Rap1 activation, suggesting that RasGRP3 might have differential affinity for these small GTPases in various glioma cells. Here, RASGRP3 is linked to central nervous system cancer.