OSBPL3 (oxysterol binding protein like 3) is a lipid transfer protein that mediates non-vesicular transport of phosphoinositide 4-phosphate (PI4P) between the plasma membrane and endoplasmic reticulum at contact sites, exchanging PI4P for phosphatidylcholine 1. It binds phosphoinositides with preference for PI(3,4)P2 and PI(3,4,5)P3, and also cholesterol and oxysterols 23. OSBPL3 associates with ER membrane protein VAPA to stimulate RRAS signaling, which attenuates integrin β1 activation and regulates actin cytoskeleton, cell polarity, and cell adhesion 45. In cancer pathology, OSBPL3 is significantly overexpressed across multiple malignancies including pancreatic, colorectal, and liver cancers, correlating with poor prognosis and reduced differentiation 678. In pancreatic cancer, high OSBPL3 expression associates with immunosuppressive microenvironments characterized by reduced CD8+ T cell infiltration and increased regulatory T cells and M2 macrophages, predicting immunotherapy resistance 6. OSBPL3 promotes pancreatic cancer malignancy through sterol metabolic reprogramming and NOTCH pathway activation, enhancing proliferation, stemness, and chemoresistance to oxaliplatin 9. In colorectal cancer, HIF-1A upregulates OSBPL3, which then activates RAS signaling to promote proliferation, invasion, and metastasis 10. Functionally, OSBPL3 knockdown reduces cancer cell viability, induces cell cycle arrest, and promotes apoptosis 8, suggesting it represents a potential therapeutic target across multiple cancer types.