SULFO-EGS is primarily used as a crosslinking agent in protein-protein interaction studies. It enables the covalent linking of interacting proteins in live cells or cell lysates, helping researchers capture transient or weak interactions that might otherwise be difficult to detect. Due to its water solubility and membrane-impermeable nature, SULFO-EGS is especially useful for targeting extracellular or cell surface protein complexes without entering the cytoplasm. It is commonly applied in structural biology and proteomics workflows, including immunoprecipitation and mass spectrometry, to stabilize and analyze protein networks. Its cleavable disulfide bond allows for controlled release of crosslinked proteins during downstream analysis, improving identification accuracy.