Oxysterol-binding protein-related protein 8

Oxysterol-binding protein-related protein 8 (OSBPL8, also called ORP-8) is a lipid transporter that mediates countertransport of phosphatidylserine and phosphatidylinositol 4-phosphate between the endoplasmic reticulum and plasma membrane (UniProt: Q9BZF1). The protein binds phosphatidylserine, PI4P, oxysterol, 25-hydroxycholesterol, and cholesterol in a regulated manner, facilitating lipid redistribution essential for membrane homeostasis.

OSBPL8 localizes to multiple subcellular compartments and plays a central role in lipid metabolism and membrane dynamics. No Mendelian disease associations are documented in UniProt for this gene.

In Alzheimer's disease, OSBPL8 is downregulated in post-mortem AD brain tissue relative to age-matched controls (Chaparral AD proteomics). Quantitative proteomics across four subcellular fractions revealed a mean log2 fold-change of −0.3603, suggesting reduced OSBPL8 abundance in the AD state. This downregulation may reflect impaired lipid homeostasis, a process increasingly implicated in AD pathogenesis.