Syndecans are type I transmembrane proteins, with an N-terminal ectodomain that contains several consensus sequences for glycosaminoglycan (GAG) attachment and a short C-terminal cytoplasmic domain. Syndecan-1 and -3 GAG attachment sites occur in two distinct clusters, one near the N-terminus and the other near the membrane-attachment site, separated by a proline and threonine-rich 'spacer'. Syndecan ectodomain sequences are poorly conserved in the family and between species, but the transmembrane and cytoplasmic domains are highly conserved. Syndecan-1 and -3 form a subfamily. Syndecan core proteins form dimers (Choi et al. 2007) and at least syndecan-3 and -4 form oligomers (Asundi & Carey 1995, Shin et al. 2012). Syndecan-1 is the major syndecan of epithelial cells including vascular endothelium. Syndecan-2 is present mostly in mesenchymal, neuronal and smooth muscle cells. Syndecan-3 is the major syndecan of the nervous system, while syndecan-4 is ubiquitously expressed but at lower levels than the other syndecans (refs in Alexopoulou et al. 2007).

Syndecans have attached heparan sulfate (HS) and to a lesser extent chondroitin sulfate (CS) chains. These allow interactions with a large number of proteins. Various enzymes involved in post-translational HS chain modifications produce unique binding motifs that selectively recognize different proteins (Tkachenko et al. 2005). It is thought that syndecans often act in concert with other receptors, e.g. integrins alphavbeta3 and alphavbeta5 cooperate with syndecan-1 during adhesion to vitronectin (Beauvais et al. 2004, McQuade et al. 2006). The relationship between syndecans and co-receptors is not well understood (Alexopoulou et al. 2007). Syndecan-null mice have subtle phenotypes when compared with mice deficient in HS chain synthesis or modification (Echtermeyer et al. 2001, Ishiquro et al. 2001, Götte et al. 2002). GPI-anchored glypicans and matrix HSPGs such as perlecan may compensate for the absence of syndecans.