When the plasma membrane contains high levels of cholesterol, GRAMD1c as well as GRAMD1a and GRAMD1b move to sites of contact between the plasma membrane and the endoplasmic reticulum.[6] GRAMD1 proteins then facilitate the transport of cholesterol into the endoplasmic reticulum.[5][6] Reduction of GRAMD1B and GRAMD1C suppresses the onset of a form of non-alcoholic fatty liver disease, non-alcoholic steatohepatitis (NASH) in mice.[5] The VASt domain is responsible for binding cholesterol while the GRAM domain determines the location of the protein through sensing of cholesterol and binding partially negatively chargedlipids in the plasma membrane, especially phosphatidylserine.[6][7]
