PLA2G12B drives expansion of triglyceride-rich lipoproteins. Vertebrates transport hydrophobic triglycerides through the circulatory system by packaging them into triglyceride-rich lipoproteins (TRLs). However, the mechanism by which triglycerides are loaded onto these particles remains unclear. Mutations in PLA2G12B disrupt lipoprotein homeostasis, but its role in this process is not well understood. This study reveals that PLA2G12B channels lipids from the endoplasmic reticulum (ER) lumen into nascent lipoproteins, promoting efficient lipid secretion and preventing excessive intracellular lipid accumulation. PLA2G12B is calcium-dependent and tightly associated with the ER membrane. It is also associated with a reduced risk of atherosclerosis in mutant mice, suggesting an evolutionary tradeoff between triglyceride transport and cardiovascular disease risk. TRLs are predominantly composed of triglycerides, which account for more than 60% of the particle mass. They are secreted from the liver as very-low-density lipoproteins (VLDL) and from the intestine as chylomicrons (CM). Secreted TRLs are digested by vascular lipases, forming smaller triglyceride-poor species. The evolution of TRLs in vertebrates was essential for efficient transport of metabolic energy between tissues. However, TRLs can also lead to ectopic lipid accumulation in the arterial wall and atherosclerosis. MTP mediates lipoprotein production by transferring lipids from the ER to APOB. It can also create APOB-free lipid micelles called luminal lipid droplets (LLDs). The biological function of LLDs is unclear, but they may fuse with nascent TRLs, delivering lipids before secretion. TRL expansion occurs in two phases: an initial lipidation step forming small nascent particles and a second phase of rapid lipidation creating mature TRLs. This second phase is not blocked by MTP inhibitors, suggesting a distinct mechanism. TRL expansion appears to occur in two phases. The first phase involves the direct transfer of a small amount of lipids to APOB by MTP, forming a small nascent particle with densities similar to high-density lipoproteins (HDL). Subsequently, a second phase of lipidation occurs, where a large amount of lipids are rapidly added to the particle core, creating a mature TRL. This second phase of lipidation is not blocked by inhibitors of MTP lipid transfer activity, suggesting it proceeds through a distinct mechanism. Triglycerides are energy-dense metabolic fuels, carrying more than twice the energy per gram as carbohydrates and proteins. The evolution of TRLs enabled vertebrates to transport metabolic energy between tissues with unprecedented efficiency. However, introducing TRLs into the bloodstream can also result in ectopic accumulation of lipPLA2G12B drives expansion of triglyceride-rich lipoproteins. Vertebrates transport hydrophobic triglycerides through the circulatory system by packaging them into triglyceride-rich lipoproteins (TRLs). However, the mechanism by which triglycerides are loaded onto these particles remains unclear. Mutations in PLA2G12B disrupt lipoprotein homeostasis, but its role in this process is not well understood. This study reveals that PLA2G12B channels lipids from the endoplasmic reticulum (ER) lumen into nascent lipoproteins, promoting efficient lipid secretion and preventing excessive intracellular lipid accumulation. PLA2G12B is calcium-dependent and tightly associated with the ER membrane. It is also associated with a reduced risk of atherosclerosis in mutant mice, suggesting an evolutionary tradeoff between triglyceride transport and cardiovascular disease risk. TRLs are predominantly composed of triglycerides, which account for more than 60% of the particle mass. They are secreted from the liver as very-low-density lipoproteins (VLDL) and from the intestine as chylomicrons (CM). Secreted TRLs are digested by vascular lipases, forming smaller triglyceride-poor species. The evolution of TRLs in vertebrates was essential for efficient transport of metabolic energy between tissues. However, TRLs can also lead to ectopic lipid accumulation in the arterial wall and atherosclerosis. MTP mediates lipoprotein production by transferring lipids from the ER to APOB. It can also create APOB-free lipid micelles called luminal lipid droplets (LLDs). The biological function of LLDs is unclear, but they may fuse with nascent TRLs, delivering lipids before secretion. TRL expansion occurs in two phases: an initial lipidation step forming small nascent particles and a second phase of rapid lipidation creating mature TRLs. This second phase is not blocked by MTP inhibitors, suggesting a distinct mechanism. TRL expansion appears to occur in two phases. The first phase involves the direct transfer of a small amount of lipids to APOB by MTP, forming a small nascent particle with densities similar to high-density lipoproteins (HDL). Subsequently, a second phase of lipidation occurs, where a large amount of lipids are rapidly added to the particle core, creating a mature TRL. This second phase of lipidation is not blocked by inhibitors of MTP lipid transfer activity, suggesting it proceeds through a distinct mechanism. Triglycerides are energy-dense metabolic fuels, carrying more than twice the energy per gram as carbohydrates and proteins. The evolution of TRLs enabled vertebrates to transport metabolic energy between tissues with unprecedented efficiency. However, introducing TRLs into the bloodstream can also result in ectopic accumulation of lip