Abstract
Thermal proteome profiling (TPP) is an innovative technique that uses the principle of protein thermal stability to identify potential protein interaction partners. Employing quantitative mass spectrometry, TPP measures protein stability across the proteome, offering a comprehensive snapshot of protein interactions in a single experiment. When studying protein-protein interactions (PPI), TPP leverages changes in apparent protein melting temperatures to identify transient and weak interactions that most traditional PPI detection methodologies struggle to measure. This review discusses current TPP methodologies, the challenges of interpreting the resulting complex datasets, and opportunities to deepen and improve PPI networks. By advancing our grasp of intricate protein interactions, TPP promises to illuminate the molecular basis of diseases and drive the discovery of novel therapeutic targets.