Transmembrane 6 superfamily member 2 (TM6SF2)

Transmembrane 6 superfamily member 2 (TM6SF2) is a multi-pass transmembrane protein primarily expressed in the liver and intestine, encoded on chromosome 19p12. TM6SF2 plays a key role in hepatic lipid metabolism by regulating the secretion of triglyceride-rich lipoproteins (TRLs) and modulating intracellular triglyceride content. Loss-of-function variants, such as E167K, are strongly associated with increased hepatocellular triglyceride accumulation (liver steatosis) and increased risk of nonalcoholic fatty liver disease (NAFLD), hepatic fibrosis, and, in some cases, hepatocellular carcinoma. Furthermore, TM6SF2 regulates the stability of apolipoprotein B (APOB), which is critical for very-low-density lipoprotein (VLDL) assembly and secretion. TM6SF2 also has roles in intestinal barrier integrity and lipid export, likely via interactions with proteins such as FABP5. Its molecular function is not fully elucidated, but evidence points to a role in ER/Golgi-associated lipid transport and lipoprotein secretion, positioning TM6SF2 as a genetic and potentially therapeutic target in metabolic and liver diseases[1][2][3][5].

Other names

TM6SF2Lpr4transmembrane 6 superfamily member 2

Not fully established; functional disruption and gene variants (most notably E167K) modulate liver triglyceride export and storage by affecting TRL secretion, influencing APOB protein stability and lipid metabolism[1][3][5].