Role of Oxysterol-Binding Protein Family in Cholesterol Metabolism and Cancer Progression: A Review

Yu Wu; Xinhui Lv; Jiyuan Yang; Sicong Liu; Yafang Chen; Ziwen Yuan; Xudong Wang

doi:10.12659/MSM.949032

21 January 2026 : Review article

Role of Oxysterol-Binding Protein Family in Cholesterol Metabolism and Cancer Progression: A Review

Yu Wu^{ABCDEF 1}, Xinhui Lv^{BC 1}, Jiyuan Yang^{BC 1}, Sicong Liu^{C 1}, Yafang Chen^{A 1}, Ziwen Yuan^{F 1}, Xudong Wang^{AEG 2*}

DOI: 10.12659/MSM.949032

Med Sci Monit 2026; 32:e949032

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Introduction Major Structural Features of ORPs Functional Features of ORPs ORPs and Cancer ORPs and Non-Cancer Diseases Future Directions Conclusions References

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Table 1 Classification of oxysterol-binding proteins (ORPs), their subcellular localization, and their transport of lipids.

	Classification	Main structure	Subcellular localization	Lipids transported
OSBP	I	PH, FFAT, ORD	n/a	OSBP-mediated countertransport of ER cholesterol for TGN PI4P []⁵⁶
ORP1	II	ORP1L; PH, FFAT, ORD, ANK; ORP1S; ORD	Late endosomes/LEL and the ER []⁶³	LDL-derived cholesterol []⁶³
ORP2	II	FFAT, ORD	n/a	Cholesterol transport from lysosomes to the PM []⁶⁴
ORP3	III	PH, FFAT, ORD	ER-PM []⁶⁵	n/a
ORP4	I	ORP4L; PH, FFAT, ORD; ORP4S; FFAT, ORD	n/a	n/a
ORP5	IV	PH, ORD, TM	ER-PM []⁶⁶	The translocation of PS from the cortical ER to the PM []⁶⁶
ORP6	III	PH, FFAT, ORD	ER, ER-PM []⁶⁷	n/a
ORP7	III	PH, FFAT, ORD	n/a	n/a
ORP8	IV	PH, ORD, TM	ER-PM []⁶⁶	The translocation of PS from the cortical ER to the PM []⁶⁶
ORP9	V	ORP9L; PH, FFAT, ORD; ORP9S; FFAT, ORD	ER-TGN MCSs []⁶⁸	ORP9 and ORP10 form a heterocomplex to transfer phosphatidylinositol 4-phosphate []⁶⁸
ORP10	VI	PH, ORD	ER-TGN MCSs []⁶⁸	ORP9 and ORP10 form a heterocomplex to transfer phosphatidylinositol 4-phosphate []⁶⁸
ORP11	VI	PH, ORD	ER-trans-Golgi membrane contact sites []⁶⁹	ORP9-ORP11 heterodimerexchanges PS for phosphatidylinositol-4-phosphate (PI(4)P) between the 2 organelles []⁶⁹
PH – pleckstrin homology domain; ORP9L – oxysterol-binding protein–related protein 9 long isoform; ORP9S – oxysterol-binding protein–related protein 9 short isoform; OSBP – oxysterol-binding protein; ORD – oxysterol-binding protein–related domain; FFAT – 2 phenylalanines (FF) within an acidic tract; TM – transmembrane; LEL – late endosomes/lysosomes; ER – endoplasmic reticulum; PM – plasma membrane; TGN – trans-Golgi network; MCSs – membrane contact sites; PI4P – phosphatidylinositol-4-phosphate; PS – phosphatidylserine.

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Role of Oxysterol-Binding Protein Family in Cholesterol Metabolism and Cancer Progression: A Review

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