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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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OSBP
oxysterol binding protein
Chromosome 11 · 11q12.1
NCBI Gene: 5007Ensembl: ENSG00000110048.13HGNC: HGNC:8503UniProt: P22059
94PubMed Papers
20Diseases
0Drugs
1Pathogenic Variants
FUNCTIONAL ROLE
Transporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingceramide transportcytosolendoplasmic reticulum-trans-Golgi network membrane contact siteneurodegenerative diseaseShort statureamyotrophic lateral sclerosisinfection
✦AI Summary

OSBP (oxysterol binding protein) is a lipid transporter that mediates cholesterol homeostasis through coordinated lipid exchange at membrane contact sites. Primary function: OSBP exchanges cholesterol and oxysterols with phosphatidylinositol 4-phosphate (PI4P) between the endoplasmic reticulum and Golgi complex, delivering sterol to the Golgi while retrieving PI4P for subsequent degradation 12. Mechanism: OSBP binds cholesterol and 25-hydroxycholesterol 34, and functions at ER-Golgi membrane contact sites through interactions with VAP-A and VAP-B anchor proteins 56. Cholesterol binding promotes formation of a PP2A-tyrosine phosphatase complex that dephosphorylates ERK1/2, while 25-hydroxycholesterol causes complex disassembly 3. OSBP also regulates cholesterol efflux by destabilizing the ABCA1 protein 7. Disease relevance: OSBP-mediated cholesterol delivery to lysosomes is critical for mTORC1 activation and growth signaling; loss of this function contributes to Niemann-Pick type C pathology, where OSBP inhibition restores autophagic function 8. Clinical significance: OSBP represents a potential therapeutic target for lipid metabolism disorders and certain viral infections that exploit host lipid homeostasis mechanisms 6.

Sources cited
1
OSBP exchanges sterol with PI4P between Golgi and ER, with PI4P subsequently degraded by SAC1/SACM1L
PMID: 24209621
2
OSBP function in sterol-PI4P countertransport between Golgi and ER membranes
PMID: 28978670
3
OSBP binds cholesterol and 25-hydroxycholesterol; cholesterol binding promotes PP2A-tyrosine phosphatase complex formation that dephosphorylates ERK1/2
PMID: 15746430
4
OSBP binds oxysterols including 25-hydroxycholesterol
PMID: 17428193
5
OSBP regulates cholesterol efflux by decreasing ABCA1 protein stability
PMID: 18450749
6
VAP-A enables lipid exchange at ER-Golgi MCS by interacting with OSBP
PMID: 36693319
7
OSBP and ORPs function as lipid-binding/transfer proteins at membrane contact sites, mediating interorganelle lipid transport and signaling
PMID: 26811291
8
OSBP delivers cholesterol across ER-lysosome contacts to activate mTORC1; OSBP inhibition restores autophagic function in Niemann-Pick type C disease
PMID: 31548609
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.53Moderate
Short statureOpen Targets
0.33Weak
amyotrophic lateral sclerosisOpen Targets
0.20Weak
infectionOpen Targets
0.06Suggestive
hemoglobin D diseaseOpen Targets
0.05Suggestive
dominant beta-thalassemiaOpen Targets
0.04Suggestive
Hemoglobin C - beta-thalassemiaOpen Targets
0.04Suggestive
hemoglobin C-beta-thalassemia syndromeOpen Targets
0.04Suggestive
hemoglobin E diseaseOpen Targets
0.04Suggestive
hemoglobin H diseaseOpen Targets
0.04Suggestive
Beta-thalassemia - X-linked thrombocytopeniaOpen Targets
0.03Suggestive
beta-thalassemia-X-linked thrombocytopenia syndromeOpen Targets
0.03Suggestive
hereditary persistence of fetal hemoglobin-sickle cell disease syndromeOpen Targets
0.03Suggestive
delta-beta-thalassemiaOpen Targets
0.03Suggestive
Alpha-thalassemia - myelodysplastic syndromeOpen Targets
0.03Suggestive
alpha-thalassemia-myelodysplastic syndromeOpen Targets
0.03Suggestive
vitamin B deficiencyOpen Targets
0.03Suggestive
Hemoglobin E - beta-thalassemiaOpen Targets
0.03Suggestive
hemoglobin E-beta-thalassemia syndromeOpen Targets
0.03Suggestive
Blackfan-Diamond anemiaOpen Targets
0.03Suggestive
Pathogenic Variants1
NM_002556.3(OSBP):c.1519C>T (p.Arg507Ter)Pathogenic
Short stature
☆☆☆☆2001→ Residue 507
View on ClinVar ↗
Related Genes
PI4KBProtein interaction97%VAPBProtein interaction97%PLEK2Protein interaction91%PLEKProtein interaction91%MOSPD2Protein interaction79%ACBD3Protein interaction79%
Tissue Expression6 tissues
Liver
100%
Brain
56%
Heart
54%
Bone Marrow
46%
Lung
36%
Ovary
35%
Gene Interaction Network
Click a node to explore
OSBPPI4KBVAPBPLEK2PLEKMOSPD2ACBD3
PROTEIN STRUCTURE
Preparing viewer…
PDB7V62 · 3.25 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.39Moderately Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.28 [0.20–0.39]
RankingsWhere OSBP stands among ~20K protein-coding genes
  • #5,096of 20,598
    Most Researched94 · top quartile
  • #4,908of 5,498
    Most Pathogenic Variants1
  • #1,939of 17,882
    Most Constrained (LOEUF)0.39 · top quartile
Genes detectedOSBP
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Biological functions of sphingomyelins.
PMID: 23684760
Prog Lipid Res · 2013
1.00
2
ER-lysosome contacts enable cholesterol sensing by mTORC1 and drive aberrant growth signalling in Niemann-Pick type C.
PMID: 31548609
Nat Cell Biol · 2019
0.90
3
Oxysterol-binding proteins.
PMID: 20213544
Subcell Biochem · 2010
0.80
4
VAP-A intrinsically disordered regions enable versatile tethering at membrane contact sites.
PMID: 36693319
Dev Cell · 2023
0.70
5
OSBP-Related Protein Family: Mediators of Lipid Transport and Signaling at Membrane Contact Sites.
PMID: 26811291
Int Rev Cell Mol Biol · 2016
0.60