OSBPL8 (oxysterol binding protein like 8) is a lipid transporter protein anchored to the endoplasmic reticulum that mediates non-vesicular lipid exchange at membrane contact sites. Its primary function involves phospholipid countertransport, specifically exchanging phosphatidylserine with phosphatidylinositol 4-phosphate (PI4P) between the endoplasmic reticulum and plasma membrane 1. OSBPL8 binds oxysterols, 25-hydroxycholesterol, and cholesterol in a ligand-sensing capacity 234, though its phospholipid transfer function appears mechanistically distinct from sterol sensing 5. Recent studies reveal OSBPL8's involvement in disease-relevant pathways. OSBPL8 operates within a GPX1-OSBPL8 axis that mediates endoplasmic reticulum-localized lipid peroxidation during ferroptosis, with knockdown promoting ROS-induced ferroptosis and tumor growth suppression 6. OSBPL8 is upregulated in liver cancer, where elevated expression correlates with poor overall survival 7. Genome-wide association studies identified OSBPL8 polymorphisms associated with high-density lipoprotein cholesterol levels 8, and gender-specific associations with kidney stone disease susceptibility linked to lipid metabolism traits 9. These findings position OSBPL8 as a critical regulator of lipid homeostasis with implications for metabolic and malignant diseases.