Pltp, known as phospholipid transfer protein, is a lipid transfer glycoprotein. It binds to and transfers amphipathic lipids between circulating lipoproteins, as well as between lipoproteins, cells and tissues [1,2,3]. It is a major determinant of the plasma levels, turnover and functionality of very low-density lipoproteins (VLDL), low-density lipoproteins (LDL) and high-density lipoproteins (HDL), thus playing a key role in lipid transfer, lipoprotein metabolism [1,3]. Additionally, it is involved in modulating the immune response and has been linked to cardiometabolic diseases, neurodegenerative diseases, immunity, and inflammation-related diseases [1,2]. Genetic models, like KO mouse models, are valuable for studying its functions.

In Pltp knockout (Pltp-/-) mouse models, Pltp deficiency attenuates high-fat-diet-induced obesity and insulin resistance. Pltp-/-mice have enhanced phosphorylated insulin receptor and Akt levels in high-fat-diet fed livers, adipose tissues, and muscles after insulin stimulation, along with more GLUT4 protein in the plasma membranes of adipocytes and muscle cells post-insulin stimulation. Also, Pltp-deficient hepatocytes have less sphingomyelins and free cholesterols in lipid rafts and plasma membranes, suggesting Pltp deficiency improves insulin sensitivity by modulating plasma membrane lipid levels [4].

In conclusion, Pltp is crucial for lipid transfer and lipoprotein metabolism. Through model-based research, especially Pltp KO mouse models, we've learned that Pltp plays a role in obesity and insulin-related metabolic diseases. Understanding Pltp's functions provides insights into the mechanisms of these diseases and potential therapeutic targets.