High-density lipoproteins, or HDLs, are macromolecular assemblies that play a key role in lipid transport, but also exert effects in endothelial function, thrombosis, and inflammation.  A recent focus by several groups on HDL function rather than HDL cholesterol revealed that efflux capacity was inversely associated with coronary artery disease.  Traditionally, cholesterol efflux is measured using a cell-based assay where cultured microphages are treated with radioactively-labeled cholesterol and subsequently exposed to a cholesterol acceptor. A recent study that appeared in the February 2019 issue of Clinical Chemistry took a completely different approach and assessed the lipoprotein proteome by using liquid chromatography and tandem mass spectrometry to measure 21 lipoprotein associated proteins.