**2.6 OSBPL4 (ORP4, OSBP2, HLM)**

**Structure, Tissue distribution and Intracellular localization:** ORP4 belongs to the subfamily I of OSBP/ORP homologues. ORP4 has an ORD, a PH domain and an FFAT motif. ORP4 shares the highest degree of similarity with OSBP and dimerizes with OSBP.

Two ORP4 cDNAs were identified: a full-length ORP4 containing a PH domain and an ORD (designated ORP4-L), and a splice variant in which the PH domain and part of the ORD were deleted (designated ORP4-S). ORP4 mRNA and protein expression overlapped partially with OSBP and were restricted to brain, heart, muscle and kidney(Wang, JeBailey et al. 2002).

Immunofluorescence localization in stably transfected Chinese hamster ovary cells showed that ORP4-S co-localized with vimentin and caused the intermediate filament network to bundle or aggregate. ORP4-L displayed a diffuse staining pattern that did not overlap with vimentin except when the microtubule network was disrupted with nocodazole.

**Molecular functions related to dyslipidemia:** Cells overexpressing ORP4S had a 40% reduction in the esterification of low-density-lipoprotein-derived cholesterol, demonstrating that ORP4 in an interaction with intermediate filaments inhibits an intracellular cholesteroltransport pathway mediated by vimentin (Wang, JeBailey et al. 2002).

ORP4L bound [3H]25-hydroxycholesterol with high affinity and specificity. However, sterol-binding or a mutation that ablated sterol-binding did not influence the interaction of GST-ORP4 with vimentin (Wyles, Perry et al. 2007). Thus the precise mechanism about what ORP4L senses to regulate intracellular cholesterol-transport pathway still remains unidentified.

**Epidemiological study:** Epidemiological study of ORP4 is not reported yet.
