Proximity-based labelling strategies for proteomic profiling have emerged as powerful tools to map the dynamic protein interaction networks relevant to physiology and pathology. Conventional proteomics methods, such as affinity purification and fractionation, are useful for the identification of protein complexes, but are often insufficient to capture transient protein–protein interactions. In the past 10 years, enzyme-catalysed proximity labelling has evolved to enable the evaluation of these interactions both in vitro and in vivo. Utilizing enzymes such as APEX (engineered ascorbate peroxidase) or TurboID, researchers have identified and explored novel protein–protein interactions, subcellular neighbourhoods and intracellular signalling pathways. By genetically fusing these enzymes, specific proteins or cellular compartments can be targeted to covalently tag proximal proteins while preserving spatiotemporal dynamics and allowing the enrichment of tagged proteins before mass spectrometry profiling. In the cardiac context, proximity-based proteomics have been used to map the interactomes of voltage-gated channels, including CaV1.2 and NaV1.5 in cardiomyocytes. The data derived from proximity-based proteomics can improve our understanding of cardiac contractility and contribute to the identification of potential therapeutic targets for conditions such as cardiac arrhythmias.

“The data derived from proximity-based proteomics can improve our understanding of cardiac contractility and contribute to the identification of potential therapeutic targets”