Mechanisms and Applications of Photocatalytic Proximity Labeling

Photocatalytic proximity labeling (PPL) is a light-controlled technique for spatially and temporally precise mapping of biomolecular interactions. This review classifies PPL platforms into small-molecule catalysts (transition metal complexes and organic chromophores) and genetically encoded photosensitizers, detailing their mechanisms and biological applications─from subcellular proteomics, cell–cell interface tagging to in vivo labeling. We compare PPL with enzyme-catalyzed methods, highlighting its advantages in spatiotemporal control, minimal genetic manipulation, and suitability for primary cells. Current challenges in PPL are also discussed. As PPL methodologies continue to evolve from mechanistic innovation toward essential biological problem-solving, they hold great promise for elucidating dynamic interaction networks with unprecedented resolution in living systems.