ARG2 (arginase 2) is a mitochondrial enzyme that catalyzes L-arginine hydrolysis to L-ornithine and urea, with primary functions in arginine bioavailability regulation and nitric oxide (NO) control 1. Unlike its hepatic counterpart ARG1, ARG2 functions mainly as a catabolic enzyme involved in polyamine and proline synthesis 1. ARG2 regulates immune responses through arginine depletion, negatively affecting CD4+ and CD8+ T cell survival and proliferation 2. Beyond enzymatic functions, ARG2 mediates non-catalytic roles in vascular biology: it inhibits endothelial autophagy and promotes endothelial cell senescence via mTORC2 signaling, independent of its enzymatic activity 1. In skeletal repair, ARG2 activation by macrophage-secreted grancalcin through plexin-B2 signaling induces skeletal stem/progenitor cell senescence and impairs fracture healing 3. ARG2 links hepatic urea and TCA cycle metabolism, with deficiency causing oxidative metabolic impairment and predisposing to fibroinflammatory liver disease 4. In diabetic kidney disease, ARG2 degradation via selective mitophagy redirects L-arginine toward NO synthesis, protecting renal function 5. ARG2 accumulation mediates contrast-induced acute kidney injury by promoting nitrosative stress through HO-1 inhibition 6. These diverse functions implicate ARG2 as a therapeutic target in metabolic, cardiovascular, and renal diseases.