CD177 is a neutrophil-specific cell surface glycoprotein that functions as a critical regulator of neutrophil activation and immune homeostasis. Mechanistically, CD177 associates with β-2 integrin complexes (CD11b/CD18) to promote TNF-primed neutrophil degranulation and superoxide production while inhibiting integrin internalization to favor adhesion over migration 12. CD177 serves as a receptor for proteinase-3 (PRTN3), facilitating its surface display on neutrophils and potentially protecting vascular integrity during neutrophil extravasation 34. CD177+ neutrophils represent a functionally distinct activated population with protective roles in inflammatory diseases. In inflammatory bowel disease, CD177+ neutrophils exhibit enhanced bactericidal capacity and IL-22 production, with CD177 deficiency leading to more severe colitis 5. Similarly, in lung ischemia-reperfusion injury, CD177+ neutrophils drive pathological inflammation through elevated mitochondrial complex I activity, and targeting this pathway reduces injury 6. CD177 also appears in tumor-infiltrating regulatory T cells where it promotes immunosuppression, and its blockade reduces Treg suppressive function 7. In hematopoietic stem cell transplantation, increased CD177+ neutrophil progenitors correlate with reduced acute graft-versus-host disease risk 8. Post-translational glycosylation of CD177 regulates its immunomodulatory effects, with St3gal5-mediated sialylation restricting neuroinflammation following CNS injury 9.