Oxysterol-binding protein-like 9 (OSBPL9)

Oxysterol-binding protein-like 9 (OSBPL9), also known as ORP9, is a member of the oxysterol-binding protein (OSBP) family, which consists of intracellular lipid transporters and receptors[1][5]. OSBPL9 is a cholesterol and phosphatidylserine transfer protein that regulates Golgi structure, lipid homeostasis, and intracellular signaling, notably acting as a negative regulator of Akt phosphorylation—a key pathway in cell survival and proliferation[1][3][5]. It exists as two main isoforms (ORP9L and ORP9S), differing in their ability to bind specific phospholipids and localize within the cell, enabling exchange of phosphatidylserine with PI4P at membrane contact sites, in particular between the endoplasmic reticulum and trans-Golgi network[3][5]. Variants in OSBPL9 have been genetically linked to neurodevelopmental syndromes, including intellectual disability and congenital brain malformations, suggesting an essential role in nervous system development and lipid metabolism[3][5]. Deficiency or disruption of OSBPL9 function can affect sphingomyelin synthesis, cholesterol distribution, and cellular growth, but as of this writing, there are no therapeutic drugs specifically targeting this protein[3][5].

Other names

Oxysterol-binding protein-related protein 9ORP9OSBP4ORP-9OSBP-related protein 9

Not established for drugs, but mechanistically, OSBPL9 proteins mediate non-vesicular lipid transport and signaling events, acting as negative regulators of Akt signaling and influencing lipid composition in cellular membranes[1][3][4][5].