COG5 is a subunit of the conserved oligomeric Golgi (COG) complex, an eight-subunit peripheral Golgi protein essential for normal Golgi function and intracellular membrane trafficking 1. COG5 forms a stable subcomplex with COG7 through a conserved CATCHR-fold interface 2, and this interaction is critical for COG complex assembly and function 3. The protein mediates retrograde vesicle transport within the Golgi apparatus and regulates glycoconjugate synthesis, including both N-glycan and O-glycan processing 4. COG5 dysfunction causes congenital disorder of glycosylation type 2I (COG5-CDG), a multisystem disease characterized by intellectual disability, hypotonia, developmental delay, seizures, microcephaly, and sensory defects 5. Pathogenic COG5 variants disrupt protein stability and solubility, impairing COG5-COG7 interaction 3. Recent findings reveal that COG5 extends beyond glycosylation function: COG5 deficiency disrupts cellular copper homeostasis, leading to impaired mitochondrial oxidative phosphorylation, particularly complex I assembly defects, and has been associated with Leigh syndrome 6. COG5 also influences cellular stress responses and senescence through Golgi functional integrity 7. Genome-wide association studies identify COG5 variants associated with sleep duration and pleiotropic effects on cardiovascular and neuropsychiatric traits 8.