LCN2 is an iron-trafficking protein that regulates cellular iron homeostasis through binding to siderophores and interaction with the SLC22A17 receptor. The iron-bound form increases intracellular iron, while the iron-free form chelates iron and promotes its export, thereby controlling intracellular iron concentration and triggering apoptosis when iron levels are depleted. Beyond iron metabolism, LCN2 participates in innate immunity by sequestering bacterial siderophores, including those from M. tuberculosis, limiting pathogen proliferation. LCN2 dysregulation is implicated in multiple disease contexts with contradictory roles. In oral squamous cell carcinoma, LCN2 promotes EGFR recycling and activation, supporting tumor growth and metastasis; silencing LCN2 reduces proliferation and metastasis in preclinical models 1. Similarly, in lung adenocarcinoma, high LCN2 correlates with worse prognosis and advanced disease stages 2. In leptomeningeal metastases, cancer cells exploit the LCN2/SLC22A17 system to sequester limited iron from the cerebrospinal fluid microenvironment 3. In lung cancer cachexia, neutrophil-derived LCN2 induces ferroptosis in adipose and muscle tissues, driving tissue wasting 4. Conversely, in gastric cancer, tumor-secreted LCN2 suppresses progression via autocrine inhibition of the 24p3R/JNK/c-Jun pathway, correlating with better prognosis 5. In dry age-related macular degeneration, elevated LCN2 reduces autophagy and activates ferroptosis in retinal pigment epithelium; monoclonal antibody neutralization rescues retinal function 6. LCN2 also contributes to inflammatory diseases: in psoriasis, LCN2 synergizes with TWEAK signaling to promote epidermal hyperplasia and inflammation 7, and in ulcerative colitis, LCN2 drives intestinal epithelial pyroptosis via the NF-κB/NLRP3/GSDMD axis 8.