Oxysterol-Binding Protein: new insights into lipid transport functions and human diseases

Oxysterol-binding protein (OSBP) mediates lipid exchange between organelles at membrane contact sites, thereby regulating lipid dynamics and homeostasis. How OSBP's lipid transfer function impacts health and disease remain to be elucidated. In this review, we first summarize the structural characteristics and lipid transport functions of OSBP, and then focus on recent progresses linking OSBP with fatty liver disease, diabetes, lysosome-related diseases, cancer and viral infections, with the aim of discovering novel therapeutic strategies for common human diseases. OSBP, a lipid-binding/transfer protein, plays an important role in lipogenesis, liposarcoma, vascular endothelial dysfunction and cholesterol efflux (Fig. A). Additionally, OSBP can be translocated to the MCS between ER and TGN or lysosome, regulating insulin granule secretion (Fig. B), mTORC1 activation (Fig. C) and ERK phosphorylation (Fig. D). All of these functions depend on the cholesterol transport ability of OSBP. Finally, in virus-infected host cells, virus hijacks the cholesterol transport pathway of OSBP for replication (Fig. E). These findings highlight the important physiological functions of OSBP and its potential to be targeted for disease treatment. [Display omitted] •Cholesterol is transported from ER to TGN by OSBP at the expense of TGN PI4P.•OSBP, CERT, PKD, Sac1 and PI4P form a complex regulatory system to maintain the balance of lipid composition in Golgi apparatus.•OSBP relies on its cholesterol transport function to be involved in lysosome-related disorders, cancer and other diseases.