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). 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.

Syndecans are also signalling molecules, interacting with cytoplasmic proteins. Syndecan-2 binds the kinase Ca2+/calmodulin associated serine/threonine kinase (CASK), a membrane-associated guanylate kinase (MAGUK) associated with intercellular junctions (Hsueh et al. 1998).