lipocalin

Lipocalins are a diverse family of small secreted proteins expressed in many tissues. They are typically 16–25 kilodaltons in mass and share a conserved structure: an eight-stranded beta-barrel that folds into a cup-shaped ligand-binding calyx. A signal peptide directs many lipocalins to secretory pathways, and the mature proteins function largely outside the cell or in secretions.

Lipocalins bind and transport a range of hydrophobic small molecules such as retinoids, fatty acids, steroids and pheromones. This binding enables solubilization, storage, and controlled delivery of ligands, influencing signaling pathways and detoxification processes. Some lipocalins also bind siderophores and contribute to innate immunity by sequestering iron, limiting microbial growth.

Notable members and roles include lipocalin-2 (NGAL), produced by neutrophils and epithelia, which binds siderophores and serves as a biomarker of kidney injury and inflammation. Lipocalin-1 (tear lipocalin) functions in ocular secretions, while beta-lactoglobulin is a major milk allergen. Retinol-binding protein 4 (RBP4) carries vitamin A, and rodents express several pheromone-transporting lipocalins such as the major urinary proteins. Across species, lipocalins show tissue-specific expression and broad ligand specificities, reflecting functional diversification within the family.

Clinical and research relevance stems from their roles in ligand transport, inflammation, and host defense. Lipocalins are studied as disease biomarkers and as templates for drug delivery and protein engineering, due to their versatile binding pockets and stability.