Lsr, also known as Lipolysis-stimulated lipoprotein receptor, is a multi-functional protein. It is essential for the assembly of epithelial tricellular tight junctions and hepatic clearance of lipoproteins. It is involved in multiple pathways and is of great biological importance in maintaining tissue homeostasis and physiological functions [1,2,3,4,5,6]. Genetic models, such as KO/CKO mouse models, have been crucial in studying its functions.

Using multiple conditional deletion mouse models, it was found that Lsr elimination in intestinal stem cells leads to the disappearance of Paneth cells without affecting other cell lineages. Mechanistically, Lsr deficiency increases YAP abundance by modulating its phosphorylation and proteasomal degradation, and Lsr protects against necrotizing enterocolitis through enhancing Paneth cell differentiation [1]. In Lsr knockout mice, the blood-brain barrier does not seal during embryogenesis, leading to leakage to small molecules, and in pathological models like experimental autoimmune encephalomyelitis and middle cerebral artery occlusion, Lsr was down-regulated, linking its loss to pathological BBB leakage [6].

In conclusion, Lsr plays key roles in maintaining epithelial barriers, including those in the intestine and blood-brain barrier. Model-based research, especially KO/CKO mouse models, has revealed its significance in intestinal epithelium homeostasis, as seen in necrotizing enterocolitis, and in blood-brain barrier formation and integrity during development and in disease conditions [1,6].