Recent Advances in Photocatalyst-Driven Protein Labeling and Proximity Mapping

Photocatalysis has emerged as a powerful strategy for controlling chemical reactivity with light, offering unique opportunities for spatial and temporal regulation. While visible-light photocatalysis was originally developed in the context of small-molecule synthesis, recent years have witnessed its rapid expansion into the selective modification of peptides and proteins under biologically compatible conditions. When photocatalysts are localized through ligands, antibodies, nanomaterials, or genetic fusion, photochemical reactivity becomes confined to defined molecular neighborhoods, giving rise to photocatalytic proximity labeling as a distinct chemical approach for probing biomolecular interactions. This review summarizes advances in photocatalyst-enabled protein modification and proximity labeling reported up to 2025. We highlight how diverse photochemical mechanisms-including single-electron transfer, energy transfer, and the generation of short-lived reactive intermediates such as radicals, carbenes, nitrenes, and singlet oxygen-have been harnessed across experimental regimes ranging from purified proteins and solid-supported platforms to living cells, tissues, and in vivo systems. Collectively, these developments establish photocatalysis as a versatile chemical framework for rational design of proximity labeling tools with tunable spatial resolution, enabling spatial encoding in biological systems and the interrogation of protein interactions within complex biological environments.