Bioconjugation Strategies for Revealing the Roles of Glycerophospholipids in Cells

Glycerophospholipids (GPLs) constitute one of the most important subclasses of phospholipids. These biomolecules are known to play multiple roles at the cellular level and are also involved as major constituents in membrane bilayers, cellular compartmentalization, and intramolecular signaling. To decipher their complex and diverse functions in cells, researchers have developed advanced bioconjugation strategies including chemical total synthesis of lipids from scratch, enabling the construction of precise lipid analogs. Bioorthogonal chemistry was also widely used to obtain lipid probes, such as fluorogenic and photoreactive GPLs. This interdisciplinary field of research merging, among other things, synthetic biology, live‐cell imaging, and bioorthogonal reactions provides unprecedented knowledge about lipid metabolism, transport, and interaction, thereby paving the way for functional studies and therapeutic innovations. Here, we summarize the approaches used to design glycerophospholipidic probes to explore lipidomics and various biological functions of GPLs.