TMEM175 and Parkinson disease: While it is tempting to hypothesize that this reduced lysosomal expression is driving the increased risk of PD with the variant, it is important to note that in the highest level of overexpression achieved for the p.M393T variant (log [MOI] 4, which did not reduce p-α-syn), the lysosomal level of TMEM175 protein was higher than the level of lysosomal TMEM175 protein seen for the intermediate WT overexpression (log [MOI] 3.5), which significantly reduced p-α-syn.