Parkinson9s disease predisposing LRRK2 kinase phosphorylates a group of Rab GTPase
proteins including Rab29, within the effector‐binding switch II motif. Previous work indicated
that Rab29, located within the PARK16 locus mutated in Parkinson9s patients, operates in a
common pathway with LRRK2. Here, we show that Rab29 recruits LRRK2 to the trans‐Golgi
network and greatly stimulates its kinase activity. Pathogenic LRRK2 R1441G/C and
Y1699C mutants that promote GTP binding are more readily recruited to the Golgi and
activated by Rab29 than wild‐type LRRK2. We identify conserved residues within the
LRRK2 ankyrin domain that are required for Rab29‐mediated Golgi recruitment and kinase
activation. Consistent with these findings, knockout of Rab29 in A549 cells reduces
endogenous LRRK2‐mediated phosphorylation of Rab10. We show that mutations that