Plasma glucosylceramide levels are regulated by and are not involved in Parkinson's disease pathogenesis.

variants and decreased glucocerebrosidase (GCase) activity are implicated in Parkinson's disease (PD). We investigated the hypothesis that increased levels of glucosylceramide (GlcCer), one of GCase main substrates, are involved in PD pathogenesis. Using multiple genetic methods, we show that not , is the main regulator of plasma GlcCer levels, yet it is not involved in PD pathogenesis. Plasma GlcCer levels were associated with PD, but not in a causative manner, and are not predictive of disease status. These results argue against targeting GlcCer in -PD and underscore the need to explore alternative mechanisms and biomarkers for PD.