Phosphoinositide-binding protein which associates with both cell and endoplasmic reticulum (ER) membranes. Can bind to the ER membrane protein VAPA and recruit VAPA to plasma membrane sites, thus linking these intracellular compartments. The ORP3-VAPA complex stimulates RRAS signaling which in turn attenuates integrin beta-1 (ITGB1) activation at the cell surface. With VAPA, may regulate ER morphology. Has a role in regulation of the actin cytoskeleton, cell polarity and cell adhesion. Binds to phosphoinositides with preference for PI(3,4)P2 and PI(3,4,5)P3. Also binds 25-hydroxycholesterol and cholesterol. Homodimer (By similarity). Interacts with RRAS (By similarity). Interacts (phosphorylated form) with VAPA (By similarity). Interacts with OSBPL6 (PubMed:30028970). Co-localizes with OSBPL6 at contact sites between the plasma membrane and the endoplasmic reticulum. Expressed in spinal ganglia. Expressed in a subset of small lymphocytes (at protein level). Expressed at higher levels in some regions of the developing central and peripheral nervous system, including hippocampal neuroepithelium, rhinencephalon, intermediate thalamus. The FFAT 2 motif is required for interaction with VAPA and regulation of the endoplasmic reticulum targeting of ORP3. The FFAT 1 motif may contribute to VAPA binding. The PH domain binds phosphoinositides, with a preference for PI(3,4)P2 and PI(3,4,5)P3. The PH domain mediates targeting to the plasma membrane. Phosphorylation is enhanced in vitro by phorbol-12-myristate-13-acetate (PMA), forskolin and calcium ionophore A23187. Phosphorylation seems to be stimulated in conditions of low cell-cell (or cell-matrix) adhesion. Belongs to the OSBP family.