CTSG (cathepsin G) is a serine protease expressed primarily in neutrophils and mast cells that functions as a multifaceted immune regulator and antimicrobial agent 12. The enzyme displays trypsin- and chymotrypsin-like specificity with preference for Phe and Tyr residues at the P1 position 1. Beyond proteolytic activity, CTSG exhibits direct antibacterial activity against both Gram-negative and Gram-positive bacteria, including N. gonorrhoeae, P. aeruginosa, L. monocytogenes, and S. aureus, independent of its protease function 34. CTSG regulates hemostasis through platelet activation via the F2RL3/PAR4 receptor and modulates thrombin receptor signaling by cleaving PAR1 at distinct sites to produce either agonistic or inhibitory effects 56. The protease enhances immune cell function by stimulating B cells, T cells, and NK cells, while also functioning as a ligand for the N-formyl peptide receptor FPR1 to enhance phagocyte chemotaxis 789. CTSG cleaves multiple immunomodulatory substrates including IL33, IL36G, and CCL5/RANTES to modulate inflammatory responses 101112. Recent evidence suggests CTSG acts as a tumor suppressor in colorectal cancer through Akt/mTOR/Bcl2 pathway inhibition 13, and genetic polymorphisms in CTSG are associated with type 1 diabetes susceptibility in Chinese populations 14.