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 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 fibronectin (Saunders & Bemfield 1988, Woods et al. 2000), vitronectin, several types of collagen (type I, III and V Koda et al. 1985), and thrombospondin-1 (Sun et al. 1989, Yoneda & Couchman 2003). It is thought that syndecans often act in concert with other receptors, e.g. alphavbeta3 and alphavbeta5 integrins cooperate with syndecan-1 during adhesion to vitronectin (Beauvais et al. 2004, McQuade et al. 2006) while alpha2beta1 and alpha6beta4 integrins cooperate with syndecans during adhesion to laminin (laminin alpha-1 Hozumi et al. 2006, laminin gamma-2, Ogawa et al. 2007). 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. Syndecans are also signalling molecules, interacting with cytoplasmic proteins. Most of the work done has involved syndecan-4 (Multhaupt et al. 2009). Zebrafish and murine syndecan-4 V regions bind the membrane lipid phosphatidylinositol 4,5 bisphosphate (PtdIns4,5P2) undergoing a shape change revealed by NMR spectroscopy (Whiteford et al. 2008). The resulting complex is able to bind protein kinase C alpha which is persistently activated in the absence of Ca2+ (Oh et al. 1997, Lee et al. 1998, Keum et al. 2004). 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). Trafficking protein particle complex subunit 4 (TRAPPC4) is a syndecan-2 interacting protein 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). 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.