[Image: see text] Through their diverse core protein modules and glycan/glycosaminoglycan moieties, proteoglycans may engage in numerous cellular and molecular interactions which are dispensable during embryogenesis, are essential for the maintenance of a healthy state and are prone to modulation in pathological conditions. Proteoglycan interactions may involve binding to other structural components of the ECM, to cell surface receptors, to membrane-associated components, and to soluble signaling molecules, which through this interaction may become entrapped in the ECM or sequestered at the cell surface. Understanding of these multiple interplays is therefore of paramount importance and requires a detailed mapping through what we define as the proteoglycome.