Xiao Wang1,2,3 and Xiao-Wei Chen1,2,3 1State Key Laboratory of Membrane Biology, Peking University, Beijing 100871, P.R. China 2Institute of Molecular Medicine, College of Future Technology, Peking University, Beijing 100871, P.R. China 3Center for Life Sciences, Peking University, Beijing 100871, P.R. China Correspondence: xiaowei_chenpku.edu.cn

APOB-containing lipoproteins are large, complex lipid carriers that ferry bulk lipids into the circulation via the secretory pathway, originating from the endoplasmic reticulum of specialized cells in the liver or the gut. Elevation of APOB-containing lipoproteins in the plasma represents a major risk factor for cardiovascular diseases. The production of these lipoproteins requires enzyme-catalyzed, cross-membrane transfer of neutral lipids and phospholipids to lipoproteins, in particular onto the structural component APOB. Transport of these lipid-bearing cargos relies on the COPII machinery and employs the transmembrane cargo receptor SURF4 and the small GTPase SAR1B, together constituting a selective transport program. Intriguingly, a number of factors implicated in lipoprotein production are also packaged into COPII vesicles and may be cotransported with APOB. These observations therefore point to a specialized produce-and-export itinerary during the secretion of these lipid-bearing cargos, warranting future investigations into this unique yet pivotal process at the crossroad of cell biology and physiology.