In the first genome-wide association study (GWAS) of vitamin D levels in continental West Africans, we identified a novel locus close to the OSBPL11 gene. OSBPL11 is implicated in adipocyte differentiation and lipid metabolism, yet its role in vitamin D physiology remains poorly understood. This study aimed to perform functional mapping of the OSBPL11 locus, describe the role of OSBPL11 in vitamin D metabolism and its broader implications in metabolic health. We conducted functional mapping and annotation of OSBPL11 using genetic databases. We performed molecular docking and in vitro protein binding assays to assess interactions between OSBPL11 and vitamin D metabolites. Additionally, metabolic consequences of OSBPL11 disruption were explored through knockout mouse model analyses. Our findings show that the lead genetic variant in our GWAS is an expression quantitative trait locus (eQTL) for OSBPL11 in African populations. According to the Harmonizome database, OSBPL11 is predominantly expressed in adipocytes, whole blood, and monocytes, and correlates with metabolic health conditions such as obesity, overnutrition, and hyperglycemia. Molecular docking results demonstrate that vitamin D metabolites bind within the oxysterol binding pocket of OSBPL11 comparably to its known oxysterol ligands. In vitro assays further suggest that vitamin D metabolites exhibit a stronger affinity to OSBPL11 than the common oxysterol, 25-hydroxycholesterol. Heterozygous OSBPL11 knockout mice exhibited increased total body fat, reduced circulating triglyceride levels, and enhanced glucose tolerance, with homozygous knockout resulting in preweaning lethality. Single-cell and multi-tissue gene expression profiles confirmed significant OSBPL11 expression in adipocytes, macrophages, and the skin. These combined findings indicate a novel function for OSBPL11 in the intracellular transport and signaling of vitamin D, with potential implications in lipid and glucose metabolism regulation.