Since 2004, defects in seven out of the eight COG subunits have been associated with human Congenital Disorders of Glycosylation (CDG)-type II, a growing family of diseases involving malfunctions in the processing of N- and O-linked glycans and resulting from mutations in proteins involved with glycosylation (Wu et al., 2004; Spaapen et al., 2005; Foulquier et al., 2006, 2007; Kranz et al., 2007; Ng et al., 2007, 2011; Paesold-Burda et al., 2009; Reynders et al., 2009; Richardson et al., 2009; Lübbehusen et al., 2010; Fung et al., 2012; Huybrechts et al., 2012; Rymen et al., 2012, 2015; Kodera et al., 2015; Table 1). Glycosylation is a highly dynamic process that occurs in the ER and Golgi which requires an estimated two percent of the human genome to encode the enzymes and trafficking components for the proper maturation of newly formed glycan chains (Freeze et al., 2014). COG deficiency can cause a redistribution of COG-dependent Golgi resident proteins, including glycosylation enzymes. Most COG-CDG patients have defects in sialylation and galactosylation, as indicated by fluorescent lectin staining of plasma membrane glycoconjugates from patient fibroblasts and MALDI-TOF mass spectrometry of serum glycoproteins (Foulquier et al., 2007; Kranz et al., 2007; Paesold-Burda et al., 2009; Reynders et al., 2009; Zeevaert et al., 2009a,b). Along with other multi-system pathologies, COG-CDG patients display mild to severe neurological defects including hypotonia, intellectual disability, developmental delays, epilepsy, and ataxia (Table 1). Specific symptoms and the severity of condition appears to relate to the COG subunit that is deficient with COG6 and COG7 patients demonstrating the most severe phenotypes (Rymen et al., 2015). Additionaly, COG defects have not yet been attributed to any other subtype of CDG.