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Protein / target

Lysosomal acid glucosylceramidase

Encoded byGBA1P04062Homo sapiensSwiss-Prot
Clinical-stage
Therapeutic maturity
2
Clinical candidates
Small-molecule tractable
Druggability
Advanced Clinical
2
Research papers

Protein at a glance

Biological role

Steryl-beta-glucosidase

Strongest disease association

Gaucher disease

Via encoding gene GBA1 · Genetic evidence · score 0.98

Therapeutic position

Clinically advancing target

Small molecules

Research activity

Emerging research

2 papers · latest 2025

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

Glucosylceramidase that catalyzes, within the lysosomal compartment, the hydrolysis of glucosylceramides/GlcCers (such as beta-D-glucosyl-(1<->1')-N-acylsphing-4-enine) into free ceramides (such as N-acylsphing-4-enine) and glucose.

View complete UniProt function annotation

Glucosylceramidase that catalyzes, within the lysosomal compartment, the hydrolysis of glucosylceramides/GlcCers (such as beta-D-glucosyl-(1<->1')-N-acylsphing-4-enine) into free ceramides (such as N-acylsphing-4-enine) and glucose (PubMed:15916907, PubMed:24211208, PubMed:32144204, PubMed:39395789, PubMed:9201993). Plays a central role in the degradation of complex lipids and the turnover of cellular membranes (PubMed:27378698). Through the production of ceramides, participates in the PKC-activated salvage pathway of ceramide formation (PubMed:19279011). Catalyzes the glucosylation of cholesterol, through a transglucosylation reaction where glucose is transferred from GlcCer to cholesterol (PubMed:24211208, PubMed:26724485, PubMed:32144204). GlcCer containing mono-unsaturated fatty acids (such as beta-D-glucosyl-N-(9Z-octadecenoyl)-sphing-4-enine) are preferred as glucose donors for cholesterol glucosylation when compared with GlcCer containing same chain length of saturated fatty acids (such as beta-D-glucosyl-N-octadecanoyl-sphing-4-enine) (PubMed:24211208). Under specific conditions, may alternatively catalyze the reverse reaction, transferring glucose from cholesteryl 3-beta-D-glucoside to ceramide (Probable) (PubMed:26724485). Can also hydrolyze cholesteryl 3-beta-D-glucoside producing glucose and cholesterol (PubMed:24211208, PubMed:26724485, PubMed:39395789). Catalyzes the hydrolysis of galactosylceramides/GalCers (such as beta-D-galactosyl-(1<->1')-N-acylsphing-4-enine), as well as the transfer of galactose between GalCers and cholesterol in vitro, but with lower activity than with GlcCers (PubMed:32144204). Contrary to GlcCer and GalCer, xylosylceramide/XylCer (such as beta-D-xyosyl-(1<->1')-N-acylsphing-4-enine) is not a good substrate for hydrolysis, however it is a good xylose donor for transxylosylation activity to form cholesteryl 3-beta-D-xyloside (PubMed:33361282). Can also metabolize plant glycosyl phytosterols such as glucosylstigmasterol (PubMed:39395789)

Subcellular location

Lysosome membrane
Domains and Gene Ontology detail (39)

Gene Ontology

  • Cendoplasmic reticulum
  • Cextracellular exosome
  • CGolgi apparatus
  • Clysosomal lumen
  • Clysosomal membrane
  • Clysosome
  • Ctrans-Golgi network
  • Fbeta-glucosidase activity
  • Fgalactosylceramidase activity
  • Fglucosylceramidase activity
  • Fglucosyltransferase activity
  • Fscavenger receptor binding

536 aa · 60 kDa · 5 isoforms

Biological roles

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Lipid & lipoprotein metabolismUniProt · GOImmune signallingGO
View supporting evidence

Lipid & lipoprotein metabolism

  • ·Glucosylceramidase that catalyzes, within the lysosomal compartment, the hydrolysis of g…
  • ·cholesterol metabolic process

Immune signalling

  • ·negative regulation of inflammatory response
  • ·negative regulation of interleukin-6 production

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene GBA1

Gene-level evidence surfaced through the gene GBA1that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Gaucher disease
0.98Well supported

Genetic evidence dominant · Open Targets 0.81

Gaucher disease type 1
0.96Well supported

Genetic evidence dominant · Open Targets 0.81

Parkinson's Disease
0.88Well supported

Genetic evidence dominant · Open Targets 0.74

View evidence synthesis (3)
Gaucher diseaseWell supported
0.98
agreement 0.891.00
Genetic70%Animal model12%Clinical10%Literature9%Genetic literaturedup

Open Targets aggregate 0.81 · 4 independent evidence families · 1 not counted as duplicate

Gaucher disease type 1Well supported
0.96
agreement 0.841.00
Genetic83%Animal model14%Literature3%Genetic literaturedup

Open Targets aggregate 0.81 · 3 independent evidence families · 1 not counted as duplicate

Parkinson's DiseaseWell supported
0.88
agreement 0.741.00
Genetic85%Literature15%Genetic literaturedup

Open Targets aggregate 0.74 · 2 independent evidence families · 1 not counted as duplicate

This ranking differs from Open Targets' own: re-weighting moves genetically-evidenced diseases above more heavily co-mentioned ones. The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations
Gaucher disease type 10.81
Gaucher disease0.81
Parkinson's Disease0.74

Drug development

2 compounds recorded · 2 in clinical development

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines.

View all recorded compounds (2)
AFEGOSTATPhase 2
AFEGOSTAT TARTRATEPhase 2

Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.

Tractability

Small moleculesStrong

Advanced Clinical and Structure with Ligand support this modality.

AntibodiesEmerging

Feasibility evidence (uniprot loc high conf and uniprot sigp or tmhmm) — no clinical-stage drug of this modality recorded.

Protein degradersEmerging

Feasibility evidence (database ubiquitination and small molecule binder) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (9)
SM · Advanced ClinicalSM · Structure with LigandSM · High-Quality LigandSM · High-Quality PocketSM · Druggable FamilyAB · UniProt loc high confAB · UniProt SigP or TMHMMPR · Database UbiquitinationPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Research activity

2 papers · to 2025

Papers linked directly to this protein. This is the protein's own literature — descriptor-derived papers are kept separate below.

Most cited

Recent

Europe PMC papers linked directly to this protein.