HT-PELSA (high-throughput peptide-centric local stability assay), a new tool developed by EMBL researchers, speeds up sample processing 100-fold, making it much more effective at finding ligand-binding regions than previous methods. Unlike the earlier version, HT-PELSA works directly with various biological samples, including crude cell, tissue, and bacterial lysates, allowing the detection of previously inaccessible protein targets, like membrane proteins – which account for the  majority of all known drug targets. By making large-scale protein research more affordable and efficient, HT-PELSA could accelerate drug discovery and transform how scientists study protein function in living systems.