Machinery inside cells can add sugar molecules to proteins and peptides to change their function and properties. So far, researchers have found sites of O-glycosylation—in which a sugar gets attached to the alcohol group of threonine and serine—on a relatively small number of peptide hormones. These hormones, which include insulin and glucagon, are involved in regulating many biological processes in the body. A team led by Katrine T. Schjoldager of the University of Copenhagen has now identified the largest number of O-linked glycosylated peptide hormones yet found (Nat. Commun. 2020, DOI: 10.1038/s41467-020-17473-1). The researchers enriched samples from humans, rodents, and pigs for O-glycosylated peptide hormones using affinity chromatography, and they identified the peptides and their glycosylation sites using mass spectrometry. Nearly one-third of the peptide hormones analyzed contained at least one site of O-glycosylation. The position of the glycosylation affects the modification’s function. Some sites improve the circulating half-life of the hormones, whereas others change where the peptides go and how they interact with their receptors. “The extent to which the sites are conserved amongst peptide family members and across species is stunning, as is localization of the sites to different regions of the peptide hormone precursors,” says Lingjun Li, an expert on peptide hormones at the University of Wisconsin–Madison, who was not involved in the work.