Application and progress of proximity labeling technology in the study of protein-protein interactions.

Protein-protein interactions are essential to almost all biological processes within cells. In recent years, proximity labeling technology has emerged as a cutting-edge approach for studying protein interactions and subcellular compartment proteomics. This technique enables labeling and capture of neighboring proteins by introducing chemical tags in the vicinity of a target protein. When combined with mass spectrometry, proximity labeling facilitates the effective identification of protein-protein interactions and proteomic landscapes of subcellular compartments with high spatiotemporal resolution. Compared to traditional methods, proximity labeling offers superior resolution, sensitivity, and real-time tracking capabilities，making it a powerful tool for investigating protein functions, interactions, and spatial proteomics within cells. In this review, we provide a comprehensive overview of the principles, classifications, and applications of proximity labeling technology, aiming to offer researchers valuable insights into this innovative methodology and to promote its broader application in cell biology, proteomics, and the study of disease mechanisms.