Prion-mediated diseases are an interesting direct application of the protein folding problem to pathology. It highlights the difference between kinetic and thermodynamic stability. The innocuous alpha helical form folds very quickly and is a metastable conformation. The disease causing beta sheet conformation, is energetically slightly more stable, however it is kinetically inaccessible (i.e. it takes a very, very long time to find this conformation randomly). This process is sped up only by catalysis, where one protein in the disease conformation helps another reach the same shape. Upon doing so, these proteins assemble and form plaques. These plaques eventually build up in the cells, disrupting normal cell processes, causing disease.

Because prions are proteins and not viruses or bacteria, they are small enough to penetrate the blood brain barrier, which normally keeps disease out of the brain. As a result, these plaques build up in neurons, causing mental illness and eventually death.