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

Leucine-rich alpha-2-glycoprotein 1 (LRG1) is a secreted glycoprotein that plays a pivotal role in promoting pathological angiogenesis, particularly in the context of cancer and vascular eye diseases (Wang et al., 2013, Nature). It functions by binding to the TGF-beta accessory receptor endoglin (ENG), which shifts TGF-beta signaling in endothelial cells from the quiescent ALK5/Smad2/3 pathway toward the pro-angiogenic ALK1/Smad1/5/8 pathway (UniProt P02750). LRG1 is highly upregulated in various malignancies, including colorectal and lung cancers, where it contributes to tumor growth, metastasis, and a suppressed immune microenvironment (O'Connor et al., 2021, Journal of Clinical Investigation). In ophthalmology, LRG1 is a key driver of neovascularization in conditions like age-related macular degeneration and diabetic retinopathy (Gow et al., 2022, Frontiers in Cell and Developmental Biology). Therapeutic strategies targeting LRG1 include monoclonal antibodies such as Magacizumab, which aim to neutralize the protein, and nucleic acid-based approaches targeting LRG1 mRNA to prevent its translation (Watson et al., 2017, Gene Therapy). Because LRG1 expression is minimal in healthy tissues but significantly elevated in diseased states, it offers a favorable safety profile for targeted therapy (O'Connor et al., 2021).

Other names

LRGHMFT1766Leucine-rich alpha-2-glycoprotein

Neutralization of the LRG1 protein or degradation of LRG1 mRNA to inhibit pathological angiogenesis and normalize TGF-beta signaling pathways.