Proteins and lipids are two major classes of transport cargos serving specific physiological functions.How these distinct biomolecules are differentially sorted through the secretory pathway,however,remains unknown.Here we report that the small GTPase SAR1B,mutated in the Chylomicron Retention Disease(CMRB),plays a rate-limiting role in specifying lipid secretion from the endoplasmic reticulum(ER).Loss of hepatic SAR1B ablated secretion of bulk lipid carried by the ApoB-containing lipoproteins(VLDLs),but didnt affect transport of proteins including Albumin,LDLR,and PCSK9.