LCN2 (lipocalin 2) is a multifunctional iron-trafficking protein that regulates iron homeostasis, innate immunity, and cellular stress responses. As an iron-binding protein, LCN2 binds siderophores (particularly 2,3-dihydroxybenzoic acid) and modulates intracellular iron levels through interaction with the SLC22A17 receptor; iron-loaded LCN2 increases intracellular iron while iron-free LCN2 depletes it 1. In innate immunity, LCN2 functions as a bacteriostatic factor by sequestering iron-bound microbial siderophores, limiting bacterial proliferation including M. tuberculosis 1. LCN2 has emerged as a critical mediator in multiple diseases. In cancer, LCN2 promotes progression across contexts: cancer cells exploit the LCN2/SLC22A17 system to acquire limiting iron in leptomeningeal metastases 2, while tissue-infiltrating neutrophils secrete LCN2 to induce ferroptosis and cachexia in lung cancer 3. In hepatocellular carcinoma, LIFR loss upregulates LCN2 via NF-κB, promoting tumorigenesis and ferroptosis resistance; LCN2 neutralization sensitizes tumors to ferroptosis therapy 4. In dry age-related macular degeneration, elevated LCN2 reduces autophagy by binding ATG4B and activates inflammasome-ferroptosis pathways 5. Post-stroke, LCN2 from neutrophil extracellular traps aggravates blood-brain barrier dysfunction through endothelial ferroptosis via the HMGB1/Nrf2/HO-1 pathway 6 and induces astrogliosis and emotional disorders 7. LCN2 shows diagnostic value as a biomarker in lung adenocarcinoma (AUC=0.818) 8, positioning it as both a therapeutic target and prognostic indicator across diseases.