Basement membrane-specific heparan sulfate proteoglycan core protein

HSPG2 encodes basement membrane-specific heparan sulfate proteoglycan core protein (HSPG), a large multifunctional protein (4,391 amino acids) that is an integral component of basement membranes. It functions as a charge-selective barrier in the glomerular basement membrane, serves as a cell attachment substrate, and plays critical roles in vascularization and heart development. HSPG also localizes acetylcholinesterase at neuromuscular junctions and possesses anti-angiogenic properties through integrin α2β1 binding and calcium-dependent mechanisms (UniProt: P98160).

HSPG2 mutations cause rare skeletal dysplasias including Schwartz-Jampel syndrome and dyssegmental dysplasia Silverman-Handmaker type (UniProt: P98160). The protein's roles in vascular function, neuromuscular organization, and extracellular matrix homeostasis position it within pathways relevant to neurodegeneration.

HSPG2 is upregulated in Alzheimer's disease brain tissue relative to age-matched controls (Chaparral AD proteomics). Analysis of post-mortem AD brain across four subcellular fractions revealed a mean log2 fold-change of 0.96, indicating increased protein abundance in the disease state. This elevation may reflect altered basement membrane composition or vascular remodeling characteristic of AD pathology.