Abundant information from human genetic studies document a clear association between increases in α-syn gene-dosing, or mutations, that exacerbate aggregation and lead to PD. In line with our hypothesis, these all are processes that can directly increase the sequestration of α-syn away from the synapse via increased aggregation kinetics (e.g., enhanced molecular crowding). Nevertheless, one would expect that if α-syn is crucial for maintaining the viability of DA neurons, human genetic data on risk of PD also would implicate mutations or polymorphisms that result in decreased α-syn. Indeed, a recent report has described exactly that (Markopoulou et al., 2014). The dinucleotide repeat REP1 is positioned upstream of the SNCA transcription start site. Polymorphisms at this site are associated with either increased or decreased SNCA expression. Contrary to the investigator's hypothesis that polymorphisms associated with decreased expression of α-syn would be associated with decreased risk of PD, these low α-syn individuals exhibited increased risk of developing PD as well as worse motor and cognitive outcomes.