Heparan Sulfate Proteoglycans: Master Regulators of Cellular Signaling, Tissue Development, and Neural Function

Abstract

ABSTRACT This narrative review examines the essential roles of heparan sulfate proteoglycans (HSPGs) in brain development, synaptic function, axonal guidance, synapse formation and stabilization, and the establishment of correctly interconnected neural networks. Distinct HSPG profiles help shape precise neural circuits, whereas HSPG dysregulation is associated with impaired neurodevelopmental processes, cognitive decline, and pathological changes in brain tissues. These findings emphasize the importance of HSPGs in normal brain function and in disease‐associated tissue dysfunction. HSPGs are a diverse group of proteins with critical roles in the CNS and PNS, including synaptic function, neurodevelopment, neurodegeneration, cell migration, and regulation of neuroprogenitor stem cell niches in the subventricular ependymal zone and subgranular dentate gyrus. Together, the diverse functions of HSPGs place them as master regulators of tissue form and function in health and disease.