Plasminogen (PLG) is a circulating zymogen that serves as the precursor to plasmin, a broad-spectrum serine protease with critical roles in fibrinolysis and tissue homeostasis 1. PLG is activated on cell surfaces through interaction with plasminogen receptors, particularly Plg-RKT, which tethers PLG via C-terminal lysine residues and promotes its conversion to the active plasmin protease 2. This cell surface activation enables localized proteolytic activity that facilitates extracellular matrix degradation, immune cell migration, and inflammatory resolution 3. Beyond hemostasis, PLG participates in pathological processes: severe hypoplasminogenemia causes ligneous conjunctivitis and pseudomembraneous lesions due to impaired fibrin clearance 1, while elevated PLG expression promotes hepatocellular carcinoma progression through enhanced anoikis resistance and cell migration 4. In gastric cancer, PLG expression inversely correlates with immune cell infiltration, suggesting immunosuppressive function 5. Periodontal disease associations highlight PLG's importance in wound healing; congenital PLG deficiency increases periodontitis risk, and genetic variants at PLG interact with other loci to regulate wound healing processes 67. Additionally, PLG enhances dengue virus type 2 infection in mosquito vectors [UniProt reference]. These findings establish PLG as a multifunctional protein with roles spanning hemostasis, inflammation resolution, tissue repair, and disease pathogenesis.