LRG1, leucine-rich α-2 glycoprotein 1, is a secreted glycoprotein. It has been linked to modulating the TGFβ signalling pathway, which is involved in various biological processes such as cell growth, differentiation, and immune response. Although constitutively expressed by hepatocytes and neutrophils, Lrg1 -/- mice initially showed no overt phenotypic abnormality, but emerging data suggest its role in innate immunity and tissue integrity. Genetic models like Lrg1 knockout mice are valuable for studying its functions [1].

In various disease conditions, Lrg1 has been shown to play significant roles. In obesity-induced metabolic diseases, Lrg1 deficiency in mice alleviated diet-induced hepatosteatosis, obesity, and insulin resistance as it promotes hepatosteatosis and inhibits hepatic insulin signalling [2]. In diabetic kidney disease, Lrg1 ablation attenuated diabetes-induced glomerular angiogenesis, podocyte loss, and glomerulopathy, indicating its role in promoting disease progression [3]. In cerebral ischemia-reperfusion injury, Lrg1 knockout reduced cerebral edema, infarct size, and improved neurological function, suggesting it mediates pathological processes [4]. In atherosclerosis, Lrg1 knockout mice showed delayed atherogenesis progression, as Lrg1 promotes macrophage M1-like polarization [5].

In conclusion, Lrg1 is a multifunctional molecule involved in several disease-related biological processes. Studies using Lrg1 knockout mouse models have revealed its role in diseases such as obesity-related metabolic diseases, diabetic kidney disease, cerebral ischemia-reperfusion injury, and atherosclerosis, highlighting its potential as a biomarker and therapeutic target for these conditions.