Paragraph: Background: Lactoferrin (Lf) is an 80 kDa iron-binding glycoprotein of the transferrin family. It is abundant in milk and in most biological fluids and is a cell-secreted molecule that bridges innate and adaptive immune function in mammals. Its protective effects range from anticancer, anti-inflammatory and immune modulator activities to antimicrobial activities against a large number of microorganisms. This wide range of activities is made possible by mechanisms of action involving not only the capacity of Lf to bind iron but also interactions of Lf with molecular and cellular components of both hosts and pathogens. Scope of review: This review summarizes the activities of Lf, its regulation and potential applications. Major conclusions: The extensive uses of Lf in the treatment of various infectious diseases in animals and humans has been the driving force in Lf research however, a lot of work is required to obtain a better understanding of its activity. General significance: The large potential applications of Lf have led scientists to develop this nutraceutical protein for use in feed, food and pharmaceutical applications. This article is part of a Special Issue entitled Molecular Mechanisms of Iron Transport and Disorders. j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / b b a g e n primates, 7 even-toed ungulates, 1 pig, 1 cat, and 1 mouse. Pairwise sequence identities ranged from a minimum of~78% to nearly 100%. The main outliers in this group were Lfs from primates, in which human and chimpanzee are quite similar (95-98%) when compared to orangutan (79%). On the other hand, horse and camel; pig, cow, yak, water buffalo, bull, and goat Lfs share 81 and 78% of sequence identity respectively when compared to human Lf as outgroup. The sequence relationships given above show that the Lfs form a highly conserved sequence family, and also sequence identity between Lfs and other Tfs is relatively high at 60-65% [19] . A characteristic feature of Lfs is their highly basic character, with a pI typically greater than 9; this property is typically predictable from their sequence. Structurally, the feature that most readily distinguishes Lfs from Tfs is the peptide linker between the two lobes, thought to have evolved from an ancient duplication event [20] , which also contains several proline residues. Lf is an 80 kDa glycosylated protein of~700 amino acids, with a high homology among species. It is comprised of a simple polypeptide chain folded into two symmetrical lobes (the N-lobe and C-lobe), which are highly homologous with one another (33-41% homology). The two lobes are connected via a hinge region containing parts of an α-helix between amino acids 333 and 343 in human Lf (hLf) [7] , which confers flexibility to the molecule [6, 7, 21] . The polypeptide chain includes amino acids 1-332, comprising the N-lobe, and 344-703, comprising the C-lobe, and it is made up of α-helix and β-pleated sheet structures that create two domains within each lobe (domains I and II) [22] . Each lobe can bind a metal atom in synergy with the carbonate ion (CO 3 −2 
 Title: Lactoferrin a multiple bioactive protein: An overview ☆
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