Section of Molecular Neurogenetics, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA *Author for correspondence: Tel.: +1 301 451 0901 or 301 496 0373; Fax: +1 301 402 6438; sidranse@mail.nih.gov Mutations in glucocerebrosidase (GBA1), the gene mutated in the lysosomal storage disorder Gaucher disease, are now widely accepted as an important genetic risk factor for the development of the common complex disorder Parkinson disease (PD) [1,2]. In recent years, this gene has also been implicated in dementia with Lewy bodies (DLB) [3,4] and even in the more rare disorder, multiple system atrophy (MSA). In the decade, since the link between GBA1 and PD was first appreciated, there has been enhanced recognition of the importance of this gene, and new clinical and basic science studies now appear in the literature almost weekly. While the field continues to advance our understanding of disease presentation and progression, major gaps in our understanding of the basis of the association remain. As the spectrum of synucleinopathies associated with GBA1 expands, there is a need for greater rigor in distinguishing the different parkinsonian syndromes involved. In doing so, specific neurodegenerative mechanisms may be more easily linked to particular clinical phenotypes. Initially, much of the literature focused on population studies. It took several years and thousands of genotypes before it was clearly established that in almost every cohort of patients with PD screened, between 3 and 20% of patients carried a GBA1 mutation, a rate approximately fiveto seven-times higher than age-matched controls [1,4,5]. This finding remained consistent in cohorts of Ashkenazi Jewish patients, patients from different European and South American countries, and centers around the USA. Remarkably, in v arious cohorts from Asia, where Gaucher disease is less often identified, the same frequency of mutations was seen, both among patients with PD and MSA [6,7]. Several large collaborative multi-center studies were performed before these fi ndings gained widespread acceptance [2]. In parallel with these studies focusing on PD, investigators who cared for patients in the Gaucher community began a more careful examination of their patient populations. Reports from “...careful evaluation of older patients with Gaucher disease or heterozygous carriers could help tease out factors shared by mutation carriers that do not develop parkinsonism in order to determine those factors that may play a protective role.”