HSPG2

HSPG2 is a human gene that encodes perlecan, a large secreted heparan sulfate proteoglycan that is a major component of basement membranes and the extracellular matrix. The perlecan core protein is organized into multiple domains, with domain I bearing glycosaminoglycan chains (heparan sulfate and sometimes dermatan sulfate) and the remaining domains consisting of laminin-like, EGF-like, and laminin G–type modules. This modular structure enables diverse interactions with other matrix components and cell-surface receptors.

Perlecan serves structural and regulatory roles in basement membranes, contributing to tissue integrity and the regulation of cell behavior. It binds to laminins, collagen IV, nidogens, and dystroglycan, and it can sequester and present growth factors such as fibroblast growth factors and vascular endothelial growth factor. Through these interactions, perlecan modulates cell adhesion, proliferation, differentiation, angiogenesis, and wound healing. It is particularly important in cartilaginous tissues, skeletal development, and the glomerular filtration barrier of the kidney.

Clinical significance involves mutations in HSPG2, which cause Schwartz-Jampel syndrome type 1, a rare congenital disorder characterized by myotonia, skeletal dysplasia, and joint contractures, often with distinctive facial features. The phenotype can range from mild to severe, reflecting different mutations and their impact on perlecan function. Animal models with HSPG2 disruption show defects in basement membranes and impaired angiogenesis, illustrating the gene’s essential role in development and vascular biology.

HSPG2 is widely expressed in tissues that rely on basement membranes, including cartilage, muscle, and vasculature, and its function is conserved across vertebrates.