Hspg2, also known as heparan sulfate proteoglycan 2, encodes perlecan, a multifunctional proteoglycan crucial for extracellular matrix integrity, tissue border maintenance, and regulation of various signaling pathways. It plays significant roles in many developmental processes like heart and brain formation, and is widely expressed in the musculoskeletal system [2].

In hypertrophic scar formation, TNFSF13 activates the NF-κB signaling pathway by interacting with Hspg2, regulating the proliferation, migration, fibrosis, and inflammatory response of hypertrophic scar fibroblasts. Mesenchymal stem cell-derived exosomes alleviate hypertrophic scar by inhibiting fibroblasts via the TNFSF-13/Hspg2 signaling pathway [1].

In human cardiomyocytes, perlecan (Hspg2 product) promotes structural, contractile, and metabolic development. Haploinsufficiency of Hspg2 in late-stage cardiomyocytes leads to structural, contractile, metabolic, and ECM gene dysregulation [3].

In bladder cancer, Hspg2 promotes tumor progression through the NID1/AKT signaling pathway [4].

In acute myeloid leukemia, Hspg2 overexpression is associated with poor prognosis and can be an independent prognostic biomarker [5].

Mutations in Hspg2 are associated with better immune checkpoint inhibitor outcomes in melanoma and non-small cell lung cancer, likely due to favorable immunocyte abundance and mutational burden [6].

Hspg2 may be a modifier gene for Marfan syndrome, as its expression correlates with disease severity in a mouse model [7].

Mutations in Hspg2 cause Schwartz-Jampel syndrome type 1, a rare musculoskeletal disorder [8].

Polymorphisms in Hspg2 are associated with intracranial aneurysm susceptibility [9].

In pan-cancer analysis, Hspg2 shows potential as a diagnostic and prognostic marker for bladder urothelial carcinoma and mesothelioma [10].

In conclusion, Hspg2 is essential for multiple biological processes, from development to tissue-specific functions. Its dysregulation or mutation is linked to various diseases, including fibrotic, cardiac, cancerous, and musculoskeletal disorders. Studies on Hspg2, often through mouse models, contribute to understanding disease mechanisms and developing potential therapeutic strategies for these conditions.