Heparan Sulfate, a complex and linear polysaccharide, forms a component of glycoproteins called heparan sulfate proteoglycans, abundantly expressed on the cell surface and within the extracellular matrix.

Heparan sulfate interacts with numerous proteins, including growth factors, morphogens, and adhesion molecules, and thereby regulates important developmental processes in invertebrates and vertebrates. Heparan sulfate chains regulate developmental signaling by acting as co-factors through a variety of mechanisms that include but are not limited to the maintenance of morphogen gradients and co-receptor functions [1]. Heparan sulfate proteoglycans can act as receptors for proteases and protease inhibitors regulating their spatial distribution and activity. Membrane Heparan sulfate proteoglycans act as coreceptors for various tyrosine kinase-type growth factor receptors, lowering their activation threshold or changing the duration of signaling reactions [2]. Heparan sulfate influences the binding affinity of intestinal epithelium cells to Wnt, thereby promoting activation of canonical Wnt signaling and facilitating the regeneration of small intestinal crypts after epithelial injury [3].

The FGF-2/FGFR system plays a critical role in modulating astrocytic reactivity and proliferation within the brain, an effect that is enhanced by heparan sulfate [5]. The degradation of heparan sulfate negatively impacts context discrimination during fear conditioning and reduces oscillatory network activity in the low theta band following such conditioning. Therefore, heparan sulfate is essential for maintaining neuronal excitability, thereby facilitating synaptic plasticity and learning processes [4].