This is complicated by the fact that while activation of a SOS/Shc-Grb2 complex has been associated with in vitro RIT1 activation following either NGF or PCAP stimulation of pheochromocytoma cells, biochemical analysis has yet to identify a bona fide RIT1GEF. Here, GRB2 is linked to hereditary pheochromocytoma-paraganglioma.