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 also involved in various signaling pathways such as Hippo/YAP, HDAC, AMPK, and affects cell metabolism [1,2].

Using multiple conditional deletion mouse models, it was found that Lsr elimination in intestinal stem cells leads to the disappearance of Paneth cells without influencing the differentiation of other cell lineages. Lsr deficiency increases the abundance of YAP by modulating its phosphorylation and proteasomal degradation. Lsr protects against necrotizing enterocolitis through enhancing Paneth cell differentiation in the small-intestinal epithelium [1].

In conclusion, Lsr plays crucial roles in maintaining epithelial barriers, cell proliferation, differentiation, and metabolism. The study of Lsr using KO/CKO mouse models has revealed its significance in intestinal epithelium homeostasis and necrotizing enterocolitis, providing potential therapeutic targets for this disease.