Perlecan, the major secreted proteoglycan in basal laminae, consists of a large multidomain core protein (~470 kDa) to which polysaccharides are covalently attached. The core protein is made up of multiple repeats of five distinct domains, including laminin-like LG domains (3 copies), EGF-like domains (12 copies), and Ig domains (22 copies). The many globular repeats give it the appearance of an approximately 200-nm-long string of pearls when visualized by electron microscopy; hence the name perlecan. Perlecan contains three types of covalent polysaccharide chains: N-linked chains (see Chapter 14), O-linked chains, and glycosaminoglycans (GAGs) (O-linked sugars and GAGs are discussed further in Section 20.4). GAGs are long, linear polymers of repeating disaccharides. Glycoproteins containing covalently attached GAG chains are called proteoglycans. Both the protein and the GAG components of perlecan contribute to its ability to incorporate into and define the structure and function of basal laminae. Because its multiple domains and its polysaccharide chains have distinct binding properties, perlecan binds to dozens of other molecules, including other ECM components (e.g., laminin, nidogen/entactin), cell-surface receptors, and polypeptide growth factors. Simultaneous binding to these molecules results in perlecan-mediated cross-linking. Perlecan can be found in basal laminae and in non–basal laminal ECM. The adhesion receptor dystroglycan can bind perlecan directly, via perlecan’s LG domains, and indirectly, via its binding to laminin. In humans, mutations in the perlecan gene can lead either to dwarfism or to muscle abnormalities, apparently due to dysfunction of the neuromuscular junction that controls muscle firing.