LRRK2 and Parkinson disease: The major hypothesis to explain the pathophysiology of LRRK2 pathogenic variants in PD is a gain of function that induces an increase in kinase activity and hyperphosphorylation of the substrate proteins.7, 8 Altered autophosphorylation of serine 12929 and more significantly the increased Rab proteins phosphorylation have been observed in LRRK2 pathogenic variants in cellulo and are indicators of kinase activity.8