LRRK2 and Parkinson disease: Thus, our data indicate that the balanced interplay among ARF6 activity, JIP3/4 association, and RAB phosphorylation state permits unopposed retrograde autophagosome transport in wild-type (WT) neurons, while hyperactivation of LRRK2 by PD-associated mutations leads to a regulatory imbalance, resulting in an inappropriate “tug-of-war” between dynein and kinesin.