TM6SF2 in Hepatic Lipid Metabolism and Chronic Liver Disease

Transmembrane 6 superfamily 2 (TM6SF2) was first described as a key regulator of hepatic lipid metabolism and lipoprotein secretion. Today, TM6SF2 is recognized to influence broader mechanisms in liver physiology and pathology. The protein has been linked to influence protein stability, very-low density lipoprotein (VLDL) assembly and secretion, hepatic lipid accumulation and development of Chronic liver disease (CLD). Furthermore, the TM6SF2 E167K variant has attracted scientific interest as it is associated with an increased risk of MASLD and other progressive liver diseases. This review provides an overview of the current knowledge of TM6SF2 and the E167K variant on hepatic lipid metabolism, VLDL mechanisms, protein interactions, CLD and antitumor immunity.