Glucosylceramidase beta 2 (GBA2)

Glucosylceramidase beta 2 (GBA2) is a non-lysosomal membrane-associated enzyme of the glycoside hydrolase family GH116 that hydrolyzes glucosylceramide (GlcCer) into glucose and ceramide on the cytoplasmic face of the endoplasmic reticulum and Golgi membranes[1][3][4][5]. It is ubiquitously expressed, with highest levels in liver, brain, and testis[4][5]. GBA2 also catalyzes transglucosylation, transferring glucose to cholesterol and possibly other substrates[5]. Mutations in GBA2 cause hereditary spastic paraplegia (SPG46) and autosomal recessive cerebellar ataxia, and result in glycolipid accumulation in various tissues, leading to non-lysosomal glycolipid storage diseases and fertility defects[1][3][4][5]. GBA2 is a pharmacological target for iminosugar drugs, such as miglustat, which reversibly inhibit its enzymatic activity[2][4]. Cross-talk with lysosomal glucosylceramidase (GBA1) may influence the clinical manifestations of Gaucher disease[3][4].

Other names

Non-lysosomal glucosylceramidaseKIAA1605SPG46AD035NLGaseBeta-glucosidase 2Beta-glucocerebrosidase 2Bile acid beta-glucosidase GBA2Bile acid glucosyl transferase GBA2Cholesterol glucosyltransferase GBA2Cholesteryl-beta-glucosidase GBA2Glucocerebrosidase 2Non-lysosomal cholesterol glycosyltransferase

Competitive/reversible inhibition of GBA2 enzymatic activity, blocking the breakdown of glucosylceramide; Mechanism-based enzyme inactivation (conduritol B epoxide); Selective inhibition (by iminosugars)