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 Trafficking protein particle complex subunit 4 (TRAPPC4), also known as synbindin. It appears to be involved with postsynaptic membrane trafficking (Ethell et al. 2000). Syndecan-2 expression promotes dendritic spine maturation in neurons, and requires the C2 domain (Ethell et al. 2000), suggesting that syndecan-2 and synbindin recruit intracellular vesicles to postsynaptic sites. More recently TRAPPC4 was shown to be a component of the Transport Protein Particle, involved in endoplasmic reticulum-to-Golgi transport (Fan et al. 2009).