F. Model for LRRK2 interaction with Rab protein substrates. GDP-bound Rab10 interacts with a GDI (Guanosine nucleotide dissociation inhibitor) and remain largely cytosolic. GEFs (guanine nucleotide exchange factors) facilitate the exchange of GDP for GTP to promote the endosome localization of Rab10. LRRK2 is temporarily recruited by GTP-bound active Rab10 on endosomes and dissociates from Rab10 after phosphorylation occurs, thereby facilitating substrate turnover. LRRK2 interaction and phosphorylation may block the interaction of Rab10 GAPs (GTPase-activating proteins) that would otherwise catalyze GTPase activity of Rab10 and promote Rab10 dissociation from endosomes (Liu et al., 2018). Without GAP interactions, Rab10 remains GTP-bound and associated with endosomes. Therefore, LRRK2 might prolong the association of Rab10 on endosomes in a GTP-bound form, but modified with phosphorylation that affects interactions with typical Rab10 effectors. 