Lgmn, also known as legumain, is an in vivo-active cysteine protease. It catalyzes the degradation of numerous proteins and is involved in multiple biological processes. Its functions are exerted through various routes, including impacts on the tumor-associated macrophage and neovascular endothelium in the tumor microenvironment [1].

In myocardial infarction, Lgmn-deficient mice showed exacerbated cardiac function, apoptotic cardiomyocyte accumulation, and reduced in vivo efferocytosis index, indicating that Lgmn expressed by cardiac resident macrophages promotes the clearance and degradation of apoptotic cardiomyocytes, which is crucial for inflammation resolution and tissue repair [2].

In thoracic aortic dissection (TAD), Lgmn-deficient or inhibited mice had ameliorated BAPN-induced TAD progression. Macrophage-specific deletion of Lgmn alleviated extracellular matrix degradation and VSMC phenotypic switch, suggesting Lgmn may be a target for TAD prevention and treatment [3].

In CD4+ T-cells, Lgmn deficiency attenuated hypertensive damage. TLGMNKO mice had reduced hypertension and target organ damage, as Lgmn in T-cells impaired Treg differentiation and function by degrading TRAF6, so targeting Lgmn in Tregs may be an innovative approach for hypertension treatment [4].

In conclusion, Lgmn plays essential roles in processes like efferocytosis in the heart, extracellular matrix regulation in blood vessels, and T-cell-mediated immune responses in hypertension. Gene knockout mouse models have been instrumental in revealing Lgmn's functions in these disease-related biological processes, providing potential therapeutic targets for myocardial infarction, TAD, and hypertension.