COG3 is a subunit of the conserved oligomeric Golgi (COG) complex, a multi-protein tethering machinery essential for intracellular protein trafficking 1. COG3 primarily functions in retrograde (Golgi-to-ER) vesicular transport and intra-Golgi trafficking 2, working alongside other COG subunits to mediate the recycling of Golgi glycosyltransferases back to the medial-Golgi compartment 1. The COG3 subunit is critical for maintaining proper localization and function of these enzymes during the secretory pathway 1. COG3 dysfunction causes congenital disorder of glycosylation type 2BB (COG3-CDG), a rare autosomal recessive condition characterized by impaired retrograde trafficking 2. Affected individuals present with global developmental delay, severe intellectual disability, microcephaly, epilepsy, and facial dysmorphism, with biochemical evidence showing reduced sialic acid on serum transferrin and decreased COG3/COG4 protein levels 2. Mechanistically, COG3 mutations lead to delayed retrograde recycling of vesicles in patient fibroblasts, disrupting the coordinated trafficking of glycosyltransferases from distal Golgi compartments 12. This separation of glycosyltransferases from anterograde cargo molecules results in abnormal protein glycosylation, the hallmark of this CDG subtype. Additionally, COG3 has been identified as a host factor involved in SARS-CoV-2 replication, suggesting broader roles in viral pathogenesis 3.