WITHDRAWN: The Fundamental And Pathological Importance Of Oxysterol Binding Protein And Its Related Proteins

Abstract

Oxysterol-binding protein (OSBP) and its related proteins (ORPs) are a large, essential family of eukaryotic proteins that possess an array of cell activities. The founding member of this superfamily, OSBP, was first discovered through its ability to bind to cholesterol and its oxygenated derivatives. Subsequently, it was the predominant view that the core function of OSBP/ORPs was to facilitate the non-vesicular transport of sterols and other lipids at membrane contact sites (MCS). However, more recently it has been suggested that the OSBP/ORPs also act as phosphoinositide coupled lipid sensors at these sites, where they modulate organelle lipid composition and direct the assembly of effector protein complexes. In this way the OSBP/ORP protein family acts to coordinate lipid metabolism with activities such as vesicle transport and cell proliferation. Given their multiple roles it is unsurprising that numerous pathologies are attributed to aberrant OSBP/OSBPL/ORP activity. Herein we summarise the current understanding of the cellular function(s) of OSBP and its related proteins in eukaryotes and describe how their dysfunction contributes to disease pathology.