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, including heparin-binding growth factors such as fibroblast growth factors (Kiefer et al. 1990, Bernfield & Hooper 1991, Steinfeld et al. 1996), vascular endothelial growth factors (VEGFs) and transforming growth factor-Beta (Chen et al. 2000, Ishiguro et al. 2002). Various enzymes involved in post-translational HS chain modifications produce unique binding motifs that selectively recognize different proteins (Tkachenko et al. 2005). HS chains facilitate interactions of syndecan-1 with extracellular matrix proteins, including thrombospondin-1 (Sun et al. 1989, Lebakken & Rapraeger 1996, Yoneda & Couchman 2003). 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.