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. Most of the work done has involved syndecan-4 (Multhaupt et al. 2009). The V-region of syndecan-4 interacts with the actin-bundling protein alpha-actinin (Greene et al. 2003, Choi et al. 2008, Shin et al. 2012), a direct link to the cell cytoskeleton.