biostudies-literatureUnknown5(10)Ng HKUnderstanding a protein's interactome provides crucial insight into its function and its contribution to disease. Traditional methods such as co-immunoprecipitations often fail to capture interactions that are dependent on native cellular architecture such as those found on the cellular membrane. While enzyme-based proximity labeling utilizing peroxidases or biotin ligases can achieve in situ interactome mapping, these approaches are limited by labeling radii, cellular engineering, and amino acid labeling biases. Antibody-guided µMap photoproximity labeling addresses the constraints of these alternative platforms. Here, we apply µMap photoproximity labeling to study the interactome of HER2 by using antibody-guided proximity labeling to target the endogenous protein, ablating the need for cCurrent protocolse70216https://www.ebi.ac.uk/biostudies/studies/S-EPMC12507076biostudies-literatureµMap Photoproximity Labeling on the Cell Surface.PMC12507076Ng HKSeath CPDouglas CJfalseµMap Photoproximity Labeling on the Cell Surface.Understanding a protein's interactome provides crucial insight into its function and its contribution to disease. Traditional methods such as co-immunoprecipitations often fail to capture interactions that are dependent on native cellular architecture such as those found on the cellular membrane. While enzyme-based proximity labeling utilizing peroxidases or biotin ligases can achieve in situ interactome mapping, these approaches are limited by labeling radii, cellular engineering, and amino acid labeling biases. Antibody-guided µMap photoproximity labeling addresses the constraints of these alternative platforms. Here, we apply µMap photoproximity labeling to study the interactome of HER2 by using antibody-guided proximity labeling to target the endogenous protein, ablating the need for c2025-01-01T00:00:00Z2025 Oct2026-05-07T03:18:41.664Z2026-05-07T03:12:22.258ZS-EPMC125070764106071110.1002/cpz1.70216