SAR1B is a small GTPase that functions primarily in vesicle-mediated endoplasmic reticulum (ER) to Golgi transport. In its active GTP-bound state, SAR1B inserts into the ER membrane and recruits the coat protein complex II (COPII), which assembles to sort cargos and deform membranes into transport vesicles 1. Unlike its paralog SAR1A, SAR1B specifically interacts with the cargo receptor SURF4 to mediate transport of lipid-carrying lipoproteins including APOB and APOA1, thereby regulating lipid homeostasis 23. Beyond vesicle trafficking, SAR1B functions as a leucine sensor regulating mTORC1 signaling independent of its GTPase activity; leucine deficiency promotes SAR1B-GATOR2 interaction inhibiting mTORC1, while leucine binding causes conformational changes that release this inhibition 4. SAR1B deficiency causes chylomicron retention disease (CMRD), characterized by severe lipid malabsorption, failure to thrive, hypocholesterolemia, vitamin E deficiency, elevated liver enzymes, and neurological complications 5. SAR1B also plays critical roles in cortical neuron migration and axon morphogenesis during development 6. Hepatic SAR1B inactivation causes hypocholesterolemia and atheroprotection, suggesting therapeutic potential for cardiovascular disease 3. Recent evidence indicates SAR1A can functionally compensate for SAR1B loss, proposing gene therapy approaches for CMRD treatment 7.