GBF1 is a guanine nucleotide exchange factor (GEF) that activates ADP-ribosylation factor (Arf) family proteins to coordinate membrane trafficking throughout the cell 1. Its primary function involves initiating COPI coat assembly at the endoplasmic reticulum, ERGIC, and cis-Golgi by generating activated ARF1-GTP, thereby regulating retrograde transport and Golgi organization 23. GBF1 also recruits adaptor proteins to the trans-Golgi network and participates in clathrin-dependent transport 4. Beyond classical vesicular trafficking, GBF1 regulates mitochondrial positioning through interactions with the mitochondrial protein Miro and dynein-dependent retrograde transport along microtubules 5, and maintains mitochondrial morphology 6. GBF1 dysfunction causes congenital cataracts through a mechanism involving unfolded protein response activation and enhanced autophagy in lens epithelium cells 7. Mutations in GBF1 are associated with Charcot-Marie-Tooth disease type 2GG and may contribute to Parkinson's disease susceptibility 8. Additionally, GBF1 is hijacked by RNA viruses including enterovirus and hepatitis C virus to facilitate their replication; enteroviral 3A proteins disrupt ER homeostasis by sequestering GBF1 and inhibiting ARF1 activation, inducing pathogenic unfolded protein responses 910. GBF1 function is regulated by phosphorylation, allowing dynamic responses to cellular needs 11.