Mutations had an autosomal dominant mode of transmission and when biochemical analysis showed that many mutations led to an increase in LRRK2 autophosphorylation activity5,6 as well as an increase in phosphorylation of surrogate substrates7, the notion of a gain of toxic kinase function was born to explain LRRK2’s pathophysiological mechanism(s) in PD. This evidence concerns the gene LRRK2 and Parkinson disease.