## 7 Concluding Remarks  
Glycan processing at the Golgi plays an essential role in cellular physiology and differentiation. Defects of \(N\)-and \(O\)-linked glycans have been linked to multiple human diseases including CDGs, inflammatory diseases and cancer [149]. Cancer cells often display characteristic glycosylation patterns such as abnormal core fucosylation, high mannose \(N\)-linked glycans and truncated \(O\)-glycans Tn (GalNAccal-Ser/Thr) and sialyl-Tn (STn) (Neu5 Ac\(\alpha\)2,6 GalNAccal-Ser/Thr) [83; 150]. Tumor-associated changes in glycosylation drive cancer progression and metastasis, providing novel diagnostic biomarkers and therapeutic targets [83]. Current applications of sophisticated mass spectrometry approaches in clinical diagnosis coupled with the advances in exome sequencing in patients have contributed to boosting the number of new glycosylation disorders [151].  
In this review, we have illustrated how the steps of glycan modifications are intimately connected to secretory trafficking with perturbation in Golgi glycosylation resulting from mutations in proteins required for COPI coat scaffolding, the incorporation of glycosyltransferases in vesicles and vesicle tethering. In the context of \(N\)-glycosylation GORAB, GOLPH3 and the COG complex are all required for the normal synthesis of complex glycans, with effects on sialylation of \(N\)-glycans. However, these proteins act at different steps of this process, with GORAB acting as a scaffold for the COPI coat complex, GOLPH3 regulating the incorporation of a subset group of glycosyltransferases into COPI vesicles, and the COG complex mostly being involved in vesicle tethering. However further studies should clarify the reciprocal dependence between these vesicle trafficking players in \(N\)- and \(O\)-glycosylation, and whether they display a specificity towards defined groups of glycosyltransferases and a cell-type limited function. Although the discovery of novel glycosylation disorders is increasing rapidly, genetic variants of important trafficking regulators have not been studied within the context of CDGs to date. For example, GOLPH3 and COG3 have been shown to have a role in glycosylation in model organisms and mammalian cell cultures, but they have not yet been associated with a CDG [65; 76; 81; 106]. We may expect that the potential impact of mutations in some secretory trafficking players on glycosylation is so severe that it is not compatible with viability. Studies on model organisms (e.g., zebrafish, flies, mice) provide a valuable resource with which to dissect the phenotypic consequences of glycosylation distinction in the whole organism and to identify potential therapeutic strategies for CDGs or cancer aimed at modulating secretory trafficking pathways [152].  
**Author Contributions:** Conceptualization, A.F., A.K.-G., S.S., M.G.G.; writing-original draft preparation; M.G.G.G. and A.F.; writing-review and editing, M.G.G. and A.F. All authors have read and agreed to the published version of the manuscript.  
**Funding:** This work was supported by a grant from Fondazione AIRC per la Ricerca sul Cancro (IG2017, Id. 20079) to M.G.G., A.F. was supported by a fellowship from the Fondazione Italiana per la Ricerca sul Cancro-Fondazione AIRC per la Ricerca sul Cancro (Id.19686).  
**Conflicts of Interest:** The authors declare no conflict of interest.