AGGRESCAN is a web-based software designed to predict and evaluate "hot spots" of aggregation in polypeptides. It is based on an aggregation-propensity scale for natural amino acids derived from in vivo experiments and assumes that short, specific sequence stretches modulate protein aggregation. The software identifies aggregation-prone segments in protein sequences, analyzes the effect of mutations on aggregation propensities, and compares the aggregation properties of different proteins or protein sets. AGGRESCAN has been validated against experimental data and has shown to accurately predict aggregation-prone regions in disease-related proteins. It also provides insights into the differential aggregation properties of globular proteins, natively unfolded polypeptides, amyloidogenic proteins, and proteins found in bacterial inclusion bodies. The software can facilitate the identification of therapeutic targets for anti-depositional strategies in conformational diseases and help anticipate aggregation phenomena during storage or recombinant production of bioactive polypeptides.AGGRESCAN is a web-based software designed to predict and evaluate "hot spots" of aggregation in polypeptides. It is based on an aggregation-propensity scale for natural amino acids derived from in vivo experiments and assumes that short, specific sequence stretches modulate protein aggregation. The software identifies aggregation-prone segments in protein sequences, analyzes the effect of mutations on aggregation propensities, and compares the aggregation properties of different proteins or protein sets. AGGRESCAN has been validated against experimental data and has shown to accurately predict aggregation-prone regions in disease-related proteins. It also provides insights into the differential aggregation properties of globular proteins, natively unfolded polypeptides, amyloidogenic proteins, and proteins found in bacterial inclusion bodies. The software can facilitate the identification of therapeutic targets for anti-depositional strategies in conformational diseases and help anticipate aggregation phenomena during storage or recombinant production of bioactive polypeptides.