Lipocalin 2 (LCN2) , also known as neutrophil gelatinase-associated lipocalin (NGAL) , is an essential innate immune protein that critically contributes to the pathogenesis of sepsis. Recent studies show that LCN2 affects sepsis onset and progression through multiple mechanisms, including the regulation of iron metabolism, inflammatory response, oxidative stress, and antibacterial immune response. The expression level of LCN2 was correlated with disease severity and patient prognosis, indicating its application value as a potential biomarker and therapeutic target. LCN2 also plays a significant role in sepsis-associated multi-organ injury, encompassing acute kidney injury, intestinal damage, encephalopathy, hepatic injury, myocardial damage, and lung injury. Future investigations should further elucidate its precise mechanisms and clinical utility to offer novel strategies for the early intervention and therapy of sepsis.