RIC1 forms a heterodimeric complex with RGP1 that functions as a guanine nucleotide exchange factor (GEF) for RAB6A, activating this GTPase by catalyzing GDP-to-GTP exchange 1. The RIC1-RGP1 complex is essential for efficient retrograde transport from endosomes to the Golgi compartment and participates in recycling of mannose-6-phosphate receptors 1. Structurally, RIC1-RGP1 interacts with RAB6A's nucleotide-binding domain through an uncharacterized helical RabGEF domain and uses an arrestin fold to bind RAB6A's hypervariable domain 2. RIC1 also functions as an effector of the medial Golgi RAB33B GTPase, establishing a RAB cascade between medial and trans-Golgi compartments 1. Beyond membrane trafficking, RIC1 is crucial for procollagen transport and secretion, making it essential for proper cartilage morphogenesis and craniofacial skeleton development 3. Loss of RIC1 function is associated with CATIFA syndrome, characterized by cleft lip, cataracts, tooth abnormalities, intellectual disability, facial dysmorphism, and ADHD 3. RIC1 haploinsufficiency through chromosome 9 deletions contributes to craniofacial defects and has been identified as one of 24 critical genes responsible for the majority of 9p deletion syndrome phenotypes 45.