RGP1 is a component of the RIC1-RGP1 guanine nucleotide exchange factor (GEF) complex that activates the RAB6A GTPase by catalyzing GDP-to-GTP exchange 1. This complex contains an evolutionarily conserved RabGEF domain and an arrestin fold that interact with RAB6A's nucleotide-binding and hypervariable domains, respectively 2. The RIC1-RGP1-RAB6A pathway is essential for retrograde transport of mannose-6-phosphate receptors from endosomes to the Golgi compartment, with RGP1 loss causing destabilization of RAB6A and blocking this trafficking 1. RGP1 also participates in STING trafficking regulation, where its depletion delays STING Golgi exit and enhances innate signaling 3. Structurally, RGP1 belongs to the arrestin-fold protein clan with primarily cytosolic localization 4. Notably, RGP1 was identified as a longevity gene with depleted loss-of-function mutations in centenarians, showing consistent causal effects on aging-related traits and altered expression patterns during aging 5. These findings suggest RGP1's protective role extends beyond membrane trafficking to influence healthy aging and longevity.