Gaucher disease (GD) is a human autosomal recessive disorder mainly due to mutations in the gene encoding for the lysosomal enzyme acid β-glucocerebrosidase (GCase). It is the most common lysosomal storage disorder. Endoplasmic reticulum associated degradation (ERAD) and limitation for translocation to lysosome are two main pathological factors for GD. So far, enzyme replcement therapy (ERT) and substrate reduction therapy (SRT) are approved medical treatments for type Ⅰ GD patients with non-neurological involvement. However, they are intrinsically associated with low stability in biological media as well as the impossibility to cross the blood brain barrier (BBB). GCase competitive inhibitors can bind mutant GCase in cytoplasm with low concentration substrates, induce it fold and translocate it to lysosome. In lysosome with high concentration substrates, competitive inhibitors dissociate from GCase and release it. Therefore, PCs (pharmacological chaperones) based on competitive inhibitors become the most promising drugs. According to the research on GCase PC in our group, the structure and the catalytic mechanism of GCase and related GCase PCs are introduced. Particularly, the structure and activity relationships of deoxynojirimycin, 1,5-dideoxy-1,5-imino-D-xylitol, isofagomine, aminoinositol and bicyclic iminosugar are discussed emphatically. In addition, other non-sugar derived PCs are briefly introduced. Finally, we analysize the future prospect of GCase PCs and propose the directions in development.

Contents
1 Introduction
2 Structure and catalytic mechanism of GCase
3 GCase pharmacological chaperones
3.1 Deoxynojirimycin
3.2 1,5-dideoxy-1,5-imino-D -xylitol
3.3 Isofagomine
3.4 Aminoinositol
3.5 Bicyclic iminosugar
3.6 Other non-sugar derived pharmacological chaperones
4 Conclusion and outlook