The serum levels of PGRN is significantly lower in Gaucher's disease patients.
4 GRN gene SNPs exhibit significantly higher frequencies in Gaucher's disease patients.
Both OVA-challenged and aged PGRN deficient mice develop Gaucher-like disease.
PGRN deficiency causes GCase aggregation and absence in lysosomes.
rPGRN protein is therapeutic against Gaucher's disease.
The present study revealed 1) PGRN was isolated as an unexpected molecule associated with GD in addition to GCase; 2) deficiency or insufficiency of PGRN contributes to Gaucher's disease in mice and humans; 3) PGRN is required for the lysosomal localization of GCase; 4) measuring serum levels of PGRN and detecting variants in GRN may be employed as biochemical and genetic diagnostic approaches for GD; 5) novel therapeutic utilities for treating GD may implement PGRN in addition to recombinant GCase; and 6) this study also presents an unique mouse model that mimics the cardinal signs of human GD, including the typical tubular-like lysosomes in macrophages always seen in human GD patients, but not observed in any GD animal models previously reported.