Leucine-rich alpha-2-glycoprotein 1 (LRG1)

Leucine-rich alpha-2-glycoprotein 1 (LRG1) is a secreted glycoprotein primarily produced by hepatocytes and neutrophils, characterized by a curved solenoid structure composed of leucine-rich repeats[1][4]. LRG1 is a member of the LRR protein family, and it modulates multiple signaling cascades—with a particularly well-characterized function in promoting angiogenesis by switching TGFβ signaling in endothelial cells from the canonical ALK5-driven anti-angiogenic pathway to the ALK1-Smad1/5/8 pro-angiogenic pathway through binding to endoglin[3][5]. Aberrant or elevated LRG1 expression is observed across a range of pathologies including cancer (where it drives abnormal blood vessel growth and can be targeted to normalize tumor vasculature), cardiovascular disease, inflammatory conditions, diabetes, and neurodegeneration[2][3][5]. It is detectable and stable in serum, making it a useful biomarker for several diseases. There are currently no approved drugs that target LRG1 directly, but experimental interventions (e.g., antibody inhibitors) have shown preclinical promise, particularly in oncology and ocular neovascularization. LRG1 also contributes to nervous system development, cell adhesion, and protein-protein interaction networks, and engages in additional signaling via LPHN2, affecting neurotrophic processes[1][4].

Other names

Leucine-rich alpha-2-glycoproteinLRG1LRGleucine rich alpha 2 glycoproteinHMFT17661300008B03Rik2310031E04Rik

Inhibition of LRG1 (e.g., by monoclonal antibody or ligand traps) shown experimentally to: Normalize tumor vasculature and potentiate immune/cytotoxic therapies in cancer; Modulate TGFβ signaling, especially via endoglin/ALK1/Smad1/5/8 axis in endothelial cells.