lipocalin2s

Lipocalin-2 (LCN2), also known as neutrophil gelatinase-associated lipocalin (NGAL) and siderocalin, is a secreted member of the lipocalin superfamily. It is encoded by the LCN2 gene in humans and has orthologs in many mammals, with mouse Lcn2 widely used as a model. The protein is produced by neutrophils and several epithelia, including kidney tubules and airway, adipose, and intestinal tissues.

Structure and secretion: LCN2 has the characteristic lipocalin beta-barrel fold, a signal peptide for secretion, and exists in multiple forms that can bind small hydrophobic molecules. In serum and urine it is found as free protein and in complex with matrix metalloproteinase-9 (MMP-9).

Biological role: The protein binds siderophores—iron-chelating molecules produced by bacteria—thereby sequestering iron and limiting microbial growth. It can also shuttle siderophore-iron complexes or free iron to mammalian cells via receptors such as the 24p3R (SLC22A17) and megalin (LRP2). LCN2 acts in innate immunity and iron homeostasis, and influences inflammation and tissue remodeling.

Expression and regulation: LCN2 expression is upregulated by inflammatory mediators such as IL-1β, TNF-α, and LPS, as well as by hypoxia. Neutrophils are a major source of circulating NGAL; tubular epithelial cells release it during kidney injury. Urinary NGAL is an established early biomarker of acute kidney injury.

Clinical relevance and research directions: Beyond AKI, LCN2 is studied in infections, chronic kidney disease, metabolic disorders, and cancer, where it can promote or inhibit tumor progression depending on context. Therapeutic strategies targeting LCN2 signaling or iron transport are explored in preclinical settings.