Angptl4, also known as angiopoietin-like 4, is a secreted glycoprotein with a crucial role in lipid metabolism. It is mainly expressed in adipose tissue and liver. Angptl4 inhibits lipoprotein lipase (LPL) activity, which hydrolyzes fatty acids from triglyceride-rich lipoproteins, thus promoting an increase in circulating triglyceride levels [1,2,5]. It is also involved in pathways related to metabolism, vascular homeostasis, and has been associated with various biological processes including angiogenesis, tumorigenesis, and stem cell regulation [1]. Genetic models, such as knockout (KO) mouse models, have been instrumental in studying its functions.

In a study on atherosclerotic Apoe-/-mice, injection of Angptl4 protein reduced atherosclerotic plaque size, vascular inflammation, and stabilized plaques by modulating the phenotypic transition of vascular smooth muscle cells through KLF4 downregulation [3]. In diabetic kidney disease, Angptl4 mutant mice showed protection from fibrosis, with reduced stimulator of interferon genes pathway activation, less epithelial-to-mesenchymal transition, and other beneficial changes, indicating that podocyte-and tubule-derived Angptl4 is fibrogenic in diabetic kidneys [4]. In a chronic kidney disease (CKD) rat model, Angptl4 was significantly upregulated and formed a loop with HIF-1α, being a key regulator in renal fibrosis [6].

In conclusion, Angptl4 is a multifunctional protein with essential roles in lipid metabolism, vascular stability, and fibrosis-related processes. The use of KO mouse models in research has revealed its specific functions in disease conditions such as atherosclerosis, diabetic kidney disease, and renal interstitial fibrosis, providing insights for potential therapeutic applications targeting these diseases.