Many members of the oxysterol binding protein family have been characterized in detail over the past decades, but the lipid transport and other functions of ORP7 still remain elusive. What is known about ORP7 points toward an endoplasmic reticulum and plasma membrane localized protein, which also interacts with GABARAPL2 and unlipidated LC3B, suggesting a further autophagosomal/lysosomal association. Roles of ORP7 have been suggested in cholesterol efflux, hypercholesterolemia, and macroautophagy. We performed a hypothesis-free multiomics analysis of chemical ORP7 inhibition with transcriptomics and lipidomics as well as proximity biotinylation interactomics to characterize ORP7 functions in a primary cell type, human umbilical vein endothelial cells (HUVECs). Moreover, assays on other metrics such as angiogenesis, cholesterol efflux and lipid droplet quantification were conducted. Pharmacological inhibition of ORP7 leads to an increase in gene expression related to lipid metabolism and inflammation and downregulation in genes associated with cell cycle and cell division. Lipidomic analysis revealed increases in ceramides, lysophosphaditylcholines, as well as saturated and monounsaturated triacylglycerols. Significant decreases were seen in all cholesteryl ester species as well as in some unsaturated triacylglycerols species, compatible with the detected decrease of mean lipid droplet area. Along with the reduced lipid stores, ABCG1-mediated cholesterol efflux and angiogenesis decreased. Interactomics revealed an interaction between AKT1 and ORP7. The transcriptomics results suggest an increase in prostanoid as well as oxysterol synthesis, which could be related to the overexpression of proinflammatory genes. Defective angiogenesis in HUVECs subjected to ORP7 inhibition could be the result of an unfavorable plasma membrane lipid composition and/or reduced potential for cell division.