Increased αSyn membrane binding, as occurs with some (e.g., E46K) but not other (e.g., G51D) PD-causing mutations, chronic dyshomeostasis of lipid metabolism (as in GBA1 loss-of-function mutations), and membrane trafficking defects (as have been reported for the G2019S and R1441C LRRK2 mutations41,77,78) have now each been associated with a statistically significant shift of physiological tetramers toward αSyn monomers, which can then become hyperphosphorylated and potentially aggregated. Here, LRRK2 is linked to Parkinson disease.