Oxysterol binding protein and its homologues: new regulatory factors involved in lipid metabolism.

Oxysterol binding protein was discovered in the 1980s as a cytosolic high-affinity receptor for oxysterols, but its function has remained enigmatic. Families of genes/proteins with sequence homology to oxysterol binding protein have been identified in eukaryotes from yeast to man, indicating that these proteins, denoted as oxysterol binding protein-related proteins (ORPs), serve a fundamental purpose conserved in evolution. This review discusses recent findings that provide important clues to the mode of action of these proteins. The long variant of ORP1 is induced upon differentiation of monocytes to macrophages and has capacity to enhance the trans-activation potential of liver X receptors, indicating a function in macrophage lipid metabolism. Important clues to ORP function were provided by the finding that most family members carry an endoplasmic reticulum targeting motif, while the amino-terminal regions of the proteins have targeting specificities for other organelles. Extensive splice variation occurs within the gene family, suggesting that a large number of distinct protein products are encoded. Further implications were obtained for a possible role of a family member in tumor cell metastasis. ORPs constitute a novel family of proteins implicated in cellular lipid metabolism and different aspects of cell regulation. The function of several family members is connected with cellular sterol metabolism, and there is evidence for a role of oxysterol binding protein in lipid transport from the endoplasmic reticulum. Recently, a model on the function of these proteins at membrane contact sites, specialized zones of communication between two different organelles, has been presented.