OSBPL6 encodes oxysterol binding protein-like 6 (ORP6), a lipid metabolism regulator with primary roles in cholesterol homeostasis. ORP6 localizes to endolysosomal and endoplasmic reticulum membranes, where it facilitates cholesterol trafficking and efflux between cellular compartments 1. The protein binds phosphatidylinositol-4-phosphate and related phosphoinositides via its pleckstrin homology domain, supporting phospholipid transfer functions. OSBPL6 expression is transcriptionally regulated by liver X receptor and cholesterol loading in macrophages and hepatocytes 1. Hepatic OSBPL6 expression correlates positively with plasma high-density lipoprotein cholesterol levels in healthy individuals and is reduced in atherosclerotic plaques 1. Clinically, OSBPL6 variants show genome-wide significant association with late-onset Alzheimer's disease risk (rs1347297, P=4.53×10⁻⁸) 2. Additionally, OSBPL6 genetic haplotypes associate with immune-related adverse events in immunotherapy patients, with risk allele carriers exhibiting significantly elevated rates of grade ≥2 and grade ≥3 adverse events (OR 3.02 and 3.59, respectively) 3. In liver cancer, OSBPL6 shows downregulated expression compared to normal tissue. OSBPL6 is also identified as a hub lipid metabolism gene in periodontitis pathogenesis through machine learning approaches 4. These findings establish OSBPL6 as a key regulator of lipid metabolism with broader implications for neurodegenerative, immunological, and inflammatory disease pathogenesis.