about 40% of yeast's ORPs. Ankyrin motif It is thought that it takes part in protein-protein interactions, but it is not known for certain. In some proteins, it also contributes to the localization of each protein to a membrane contact site (zone of close contact between the endoplasmic reticulum and a second organelle). Transmembrane domain It is only present in some human proteins. It is a hydrophobic region which holds the protein to the cell membrane. PH (pleckstrin homology) domain It binds phosphoinositides, usually only the ones which have low affinity and other ligands. It also recognizes organelles enriched in the PIPs. GOLD (Golgi dynamics) domain As well as Ankyrin motif, it probably mediates interactions between proteins. It is only found in one yeast protein and it is not found in any human ORP. ORD (OSBP-related domain) It contains the EQVSHHPP sequence. It has an hydrophobic pocket that binds a sterol and also contains multiple membrane binding surfaces which permit the protein to have the ability to cause liposome aggregation. Main functions As part of the Lipid Transfer proteins (LTPs) family, ORPs have different and variate functions. This functions include signaling, vesicular trafficking, lipid metabolism and nonvesicular sterol transport. ORPs have been studied in many organisms cells as human cells or yeast. In yeast, where organelle membranes are closely apposed it has been proposed that ORPs work as sterol transporters, though only a few ORPs actually bind sterols and collectively yeast ORPs are dispensable for sterol transfer in vivo. They are also part of Golgi-to-plasma membrane vesicular trafficking, but their role is not clear yet. In mammalian, ORPs participate as sterol sensors. This sensors regulate the assembly of protein complexes when cholesterol levels fluctuate. They use the following mechanisms: 1-They could extract and deliver lipids from one membrane to another. Probably at membrane contact site. 2-ORPs help establish the membrane when transient changes in the distribution of lipids occur. They add or remove lipids within different regions of the membrane. The exclusion of certain lipids in particular regions drive to processes such as membrane binding or signaling. 3-They work as lipid sensors altering interactions with other proteins due to binding or releasing lipid ligands. It occurs mainly at inally organelle contact sites. 4-The access of other lipid-binding proteins to the membrane is regulated by ORPs in two ways. One way is by presenting a lipid to a second lipid-binding protein.