Lcn2, also known as lipocalin 2, is a secreted glycoprotein produced by immune cells like neutrophils and macrophages. It has diverse functions including transporting hydrophobic ligands across cell membranes, regulating immune responses, maintaining iron balance, and promoting epithelial cell differentiation. Lcn2 is involved in multiple physiological processes and its expression is up-regulated in various human diseases and cancers [2].

In cancer cachexia, studies using mouse models have provided valuable insights. In lung cancer cachexia, LCN2 secreted by tissue-infiltrating neutrophils induces ferroptosis and wasting of adipose and muscle tissues. Inhibition of LCN2 expression significantly reduces cachexia symptoms and tissue wasting [1]. In pancreatic cancer cachexia, Lcn2-knockout mice show that Lcn2 mediates adipocyte-muscle-tumor communication and hypothermia. Therapeutic suppression of Lcn2 may minimize cachexia progression [3]. In sepsis-induced liver injury, LCN2 depletion in mice exacerbates liver injury, oxidative stress, and ferroptosis, while LCN2 overexpression ameliorates LPS-induced cell injury in an in vitro sepsis model [4].

In conclusion, Lcn2 is a multifunctional protein involved in various biological processes. Model-based research, especially using Lcn2 KO/CKO mouse models, has revealed its crucial roles in cancer cachexia and sepsis-induced liver injury. These findings contribute to understanding the mechanisms of these diseases and potentially developing new therapeutic strategies targeting Lcn2.