Gaucher’s disease (GD) is a genetic disorder characterized by loss of glucocerebrosidase activity in cells resulting in accumulation of glucocerebroside. Mutation of GBA1, which encodes the lysosomal glucocerebrosidase (GCase) in human, will lead to GD whose symptoms include deficits in liver function, skeletal disorders, and in some cases severe neurological complications. Recent human genome sequencing studies have demonstrated that genetic variations in GBA1 constitute the largest known risk factor for Parkinson’s disease. To better understand the functional consequence of glucocerebrosidase impairment, we constructed a genetic model of Gaucher’s disease in the nematode C. elegans by investigating gba loss-of-function (lf) gene family members. Biochemical assays indicate that animals with a gba-3 gene deletion lack GCase activity that can be rescued by transgenic overexpression of human GBA1. The gba-3 (lf) animals appear to be superficially wild type. Genetic crosses with a transgenic overexpression model of Parkinson’s disease utilizing human alpha-synuclein A53T overexpression found only modest changes to the ongoing neuropathology and behavior. Thus, while loss of GCase activity have severe consequences in humans, nematodes function well without such enzyme activity. Our studies suggest that C. elegans may have conserved GCase activity but find it dispensable. These results highlight the complex nature of GCases in humans yet provide a novel genetically tractable model to address questions related to its role in human diseases. Funding: This study was supported by grants from the Faculty of Science, University of Macau.