VPS35 and brain neoplasm: Indeed, overexpression of a dominant negative form of Rab5 GTPase (Rab5-DN), which blocks the fusion of endocytic vesicles with early endosomes, or a constitutively active form of Rab9 GTPase (Rab9-CA), which promotes protein retrograde trafficking from late endosomes to trans-Golgi network (TGN) or the plasma membrane (Figure 5—figure supplement 1), completely suppressed brain tumor formation in vps35 mutant brains (Figure 5B,C).