Glucocerebrosidase (acid β-glucosidase) !

Glucocerebrosidase is the lysosomal enzyme that removes glucose from glucosylceramide. Its absence causes Gaucher disease.

Updated 2026-11-01

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Key facts

Glucosylceramide + H₂O → glucose + ceramide, at acid pH inside the lysosome.
It needs saposin C (from the PSAP gene) to reach the lipid on the inner lysosomal membrane.
It does not use mannose 6-phosphate: it reaches the lysosome with the membrane protein LIMP-2.
Single-allele GBA1 variants are the most common genetic risk factor for Parkinson disease.

Active at acid pH (≈ 5), inactive at the neutral pH of the cytosol.
The transcription factor TFEB increases its synthesis along with other lysosomal enzymes.

Miglustat (N-butyl-deoxynojirimycin), the ligand in the 3D model; clinically it acts mainly by slowing glucosylceramide synthase
Isofagomine (pharmacological chaperone under study)
Conduritol B epoxide (irreversible laboratory inhibitor)

Its deficiency causes Gaucher disease (types 1, 2 and 3); the N370S (N409S) variant gives type 1 and protects against neurological damage.
Recombinant replacement enzyme is modified to expose mannoses and enter macrophages through the mannose receptor.
Carriers of GBA1 variants have a higher risk of Parkinson disease and dementia with Lewy bodies.

Think of the answer, then tap the question to see it.

Which reaction does glucocerebrosidase catalyse?

It hydrolyses glucosylceramide into glucose and ceramide inside the lysosome.

Which activator protein does glucocerebrosidase need?

Saposin C, which lifts the lipid from the membrane and presents it to the enzyme.

Why is Gaucher replacement enzyme designed with exposed mannoses?

So macrophages, the cells that store the lipid, take it up through their mannose receptor.

Which common neurodegenerative disease is linked to GBA1 variants?

Parkinson disease: GBA1 variants are its most frequent genetic risk factor.

Educational information, not medical advice. For any symptom, see a health professional.

Sources: GBA1: Lysosomal acid glucosylceramidase (human) (UniProt, 2026); GBA1 gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); 2V3D: acid-beta-glucosidase with N-butyl-deoxynojirimycin (RCSB Protein Data Bank, 2026); Glycosphingolipid metabolism (Reactome, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).

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Representative model, for educational purposes only.