From glycophenotyping by (plant) lectin histochemistry to defining functionality of glycans by pairing with endogenous lectins.

About 60 years ago, the efforts to identify blood group-specific haemagglutinins in plant extracts by broad-scale testing were beginning to make a large panel of these proteins available as laboratory tools. Their ability to 'read' cell surface signals like antibodies do was the reason for W. C. Boyd to call them lectins, from Latin legere (to read). These proteins turned out to be as widely present in nature as glycans (polysaccharides or carbohydrate chains of cellular glycoconjugates) are. Since carbohydrates have the virtue to facilitate high-density coding in a minimum of space and lectins (initially mostly from plants called phytohaemagglutinins) turned out to be receptors for glycans, their pairing made many applications possible. Most prominently, these proteins were instrumental to map glycome complexity and sites of product generation during glycan assembly in the cell. The detection of mammalian (tissue) lectins and the emerging evidence for intimate molecular recognition between this class of receptors and their (glycoconjugate) counterreceptors substantiate that understanding the rules of the sugar code is presently a major challenge.