Histidine-rich glycoprotein (HRGP) is a relatively less known glycoprotein, but it is abundant in plasma with a multidomain structure, which allows it to interact with many ligands and regulate various biological processes. HRGP ligands includes heme, Zn²⁺, thrombospondin, plasmin/plasminogen, heparin/heparan sulfate, fibrinogen, tropomyosin, IgG, FcγR, C1q. In many conditions, the histidine-rich region of HRGP strengthens ligand binding following interaction with Zn²⁺ or exposure to low pH, such as sites of tissue injury or tumor growth. The multidomain structure and diverse ligand binding attributes of HRGP indicates that it can act as an extracellular adaptor protein, connecting with different ligands, especially on cell surfaces. Also, HRGP can selectively target IgG, which blocks the production of soluble immune complexes. The most common cell surface ligand of HRGP is heparan sulfate proteoglycan, and the interaction is also potentiated by elevated Zn²⁺ concentration and low pH. Recent reports have shown that HRGP can modulate macrophage polarization and possibly regulate other physiological processes such as angiogenesis, anti-tumor immune response, fibrinolysis and coagulation, soluble immune complex clearance and phagocytosis of apoptotic/necrosis cells. In addition, it has also been reported that HRGP has antibacterial and anti-HIV infection effects and may be used as a novel clinical biomarker accordingly. This review outlines the molecular, structural and biological properties of HRGP as well as presenting an update on the function of HRGP in various physiological processes.

富含组氨酸的糖蛋白 (HRGP) 是一种相对鲜为人知的糖蛋白，但它在血浆中含量丰富，具有多域结构，这使其能够与许多配体相互作用并调节各种生物过程。HRGP配体包括血红素、Zn ²⁺、血小板反应蛋白、纤溶酶/纤溶酶原、肝素/硫酸乙酰肝素、纤维蛋白原、原肌球蛋白、IgG、FcγR、Clq。在许多情况下，HRGP 的组氨酸富集区域在与 Zn ^{2+相互作用后增强了配体结合}或暴露于低 pH 值，例如组织损伤或肿瘤生长部位。HRGP的多结构域结构和多样化的配体结合属性表明它可以作为细胞外衔接蛋白，与不同的配体连接，尤其是在细胞表面。此外，HRGP 可以选择性地靶向 IgG，从而阻止可溶性免疫复合物的产生。HRGP 最常见的细胞表面配体是硫酸乙酰肝素蛋白多糖，这种相互作用也因 Zn ^{2+升高而增强}浓度和低 pH 值。最近的报道表明，HRGP 可以调节巨噬细胞极化并可能调节其他生理过程，如血管生成、抗肿瘤免疫反应、纤维蛋白溶解和凝血、可溶性免疫复合物清除和凋亡/坏死细胞的吞噬作用。此外，也有报道称HRGP具有抗菌和抗HIV感染的作用，因此可作为一种新型的临床生物标志物。本综述概述了 HRGP 的分子、结构和生物学特性，并介绍了 HRGP 在各种生理过程中的功能更新。