The known unknowns of apolipoprotein glycosylation in health and disease

Apolipoproteins, the protein component of lipoproteins, play an important role in lipid transport, lipoprotein assembly, and receptor recognition. Apolipoproteins are glycosylated and the glycan moieties play an integral role in apolipoprotein function. Changes in apolipoprotein glycosylation correlate with several diseases manifesting in dyslipidemias. Despite their relevance in apolipoprotein function and diseases, the total glycan repertoire of most apolipoproteins remains undefined. This review summarizes the current knowledge and knowledge gaps regarding human apolipoprotein glycan composition, structure, glycosylation site, and functions. Given the relevance of glycosylation to apolipoprotein function, we expect that future studies of apolipoprotein glycosylation will contribute new understanding of disease processes and uncover relevant biomarkers and therapeutic targets. Considering these future efforts, we also provide a brief overview of current mass spectrometry based technologies that can be applied to define detailed glycan structures, site-specific compositions, and the role of emerging approaches for clinical applications in biomarker discovery and personalized medicine.