Oxysterol-binding protein (OSBP) (OSBP)

Oxysterol-binding protein (OSBP) is the founding member of a conserved family of lipid transfer proteins (ORPs/OSBPLs) that facilitate the non-vesicular transport of lipids between organelles at membrane contact sites (UniProt: P22059). OSBP primarily functions at the endoplasmic reticulum (ER)-Golgi interface, where it mediates the counter-directional exchange of cholesterol and phosphatidylinositol 4-phosphate (PI4P) (PubMed: 24855905). This activity is crucial for maintaining the lipid composition of the Golgi apparatus and supporting various cellular processes, including vesicular trafficking and signaling (PubMed: 33556339). In the context of disease, OSBP is a critical host factor for the replication of numerous plus-strand RNA viruses, such as enteroviruses and coronaviruses, which hijack OSBP to form viral replication organelles (PubMed: 25512477). Additionally, OSBP and its relative ORP4 are implicated in cancer cell proliferation and survival, making them attractive targets for antiviral and antineoplastic therapies (PubMed: 21854931). Several small molecules, collectively termed ORPphilins (e.g., OSW-1, schweinfurthins) and repurposed drugs like itraconazole, exert their effects by binding to the OSBP-related ligand-binding domain (ORD), thereby inhibiting lipid transfer or inducing protein degradation (PubMed: 26859458). These interactions disrupt the formation of viral replication complexes and impair the growth of various cancer cell lines.

Other names

OSBP1Oxysterol-binding protein 1OSBP-related proteinsORP familyOSBPL familyOxysterol-binding protein-related proteins

Inhibition of non-vesicular lipid transfer (cholesterol/PI4P exchange) at membrane contact sites, disruption of viral replication organelles, and induction of target protein degradation.