SAR1A is a small GTPase that functions primarily in endoplasmic reticulum (ER) to Golgi vesicle-mediated protein transport. The GTP-bound active form inserts into the ER membrane and recruits coat protein complex II (COPII) components, initiating vesicle budding and cargo sorting 1. SAR1A works alongside SEC16A to organize ER exit sites (ERES), specialized membrane domains where COPII-coated vesicles form. By regulating GTPase-dependent timing of COPII assembly, SAR1A controls vesicle size and cargo selection 2. Beyond its canonical secretory pathway role, SAR1A functions as a leucine sensor regulating mTORC1 signaling independent of its GTPase activity 3. Under leucine deficiency, SAR1A binds GATOR2 to inhibit mTORC1; leucine binding triggers conformational change and dissociation, permitting mTORC1 activation. Additionally, SAR1A regulates STING trafficking during innate immune responses through K27-linked oligo-ubiquitination, facilitating STING-COPII complex assembly for ER-Golgi transport and Type I interferon production 4. Clinical relevance includes SAR1A's role in osteosarcoma metastasis through RhoA/YAP pathway regulation and autophagy modulation 5, cardiac sodium channel trafficking 2, and lung cancer development via circRNA mechanisms 6. SAR1A shows functional overlap with its paralog SAR1B; genetic studies demonstrate SAR1A upregulation could therapeutically compensate for SAR1B deficiency-related chylomicron retention disease 1.