During HCV budding inside the ER lumen, apolipoproteins B and E associate with the enveloped virus. Once released into the ER, the nascent virion acquires all the components of lipoprotein (apolipoproteins and lipids) to produce LVP, the infectious form of HCV. Together with MTP, TM6SF2 may facilitate lipid loading onto the newly assembled virion during the budding and/or maturation of LVP (1). After the formation of infectious LVP, TM6SF2 may also enrich the lipid composition of HCV particles in the ER lumen (2) and/or during the secretory pathway through the Golgi apparatus or secretory vesicles (3). The extent of lipidation by TM6SF2 may be linked to viral infectivity and an important signal for efficient secretion of LVP (4).