Work

Glycogen and Glycosylation: Friends or Foes?

Year: 2026

Type: article

Abstract: Glycosylation, glycogen metabolism, and ubiquitination represent three fundamental cellular processes that are traditionally studied as distinct aspects of biology. Glycosylation and glycogen metabolism are unique carbohydrate-based pathways. The process of glycosylation generates structurally diverse glycans that regulate protein folding, cell signaling, and host-pathogen interactions, while glycogen serves as a glucose reserve essential for energy homeostasis. Emerging evidence reveals a deep mechanistic connection between these pathways, particularly in the context of brain biology and inherited metabolic diseases. Here, we present recent research linking glycosylation defects with glycogen metabolism, highlighting how changes in the shared metabolites and enzymatic pathways contribute to human health and disease. We then discuss the overlapping disease symptoms of congenital disorders of glycosylation and glycogen storage diseases, with particular emphasis on polyglucosan body-forming diseases. We also highlight the role of non-canonical ubiquitin ligase complexes such as laforin-malin and LUBAC and present emerging evidence for their potential role in the glycogen quality-control mechanism. Finally, we review current therapeutic strategies for CDGs and GSDs, including monosaccharide supplementation, glycogen synthase modulation, and gene therapy. Together, this review underscores glycogen as more than an energy store-as a key contributor to glycosylation homeostasis and cellular regulation in health and disease.

Source: Biomolecules

DOI: 10.3390/biom16060885

Authors: Rohit Sai Reddy Konada, James Osborn, Sharmistha Mitra

Institution: The University of Texas Southwestern Medical Center

Language: English

Topic: Glycogen Storage Diseases and Myoclonus

Subfield: Rheumatology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,258