Oxysterol-binding protein (OSBP) and OSBP-related proteins (ORPs) constitute a fa
mily of sterol and phosphoinositide binding proteins conserved in eukaryotes. The
mechanis
ms of ORP function have re
mained inco
mpletely understood. However, several ORPs are present at
me
mbrane contact sites and control the activity of enzy
matic effectors or asse
mbly of protein co
mplexes, with i
mpacts on signaling, vesicle transport, and lipid
metabolis
m. An increasing nu
mber of protein interaction partners of ORPs have been identified, providing clues of their involve
ment in
multiple aspects of cell regulation.
The functions assigned for mammalian ORPs include coordination of sterol and sphingolipid metabolism and mitogenic signaling (OSBP), control of ER-late endosome (LE) contacts and LE motility (ORP1L), neutral lipid metabolism (ORP2), cell adhesion (ORP3), cholesterol eggress from LE (ORP5), macrophage lipid homeostasis, migration and high-density lipoprotein metabolism (ORP8), apolipoprotein B-100 secretion (ORP10), and adipogenesis (ORP11). The anti-proliferative ORPphilin compounds target OSBP and ORP4, revealing a function of ORPs in cell proliferation and survival. The m>Saccharomyces cerevisiaem> OSBP homologue (Osh) proteins execute multifaceted functions in sterol and sphingolipid homeostasis, post-Golgi vesicle transport, as well as phosphatidylinositol-4-phosphate and target of rapamycin complex 1 (TORC1) signaling. These observations identify ORPs as coordinators of lipid signals with an unforeseen variety of cellular processes.