In agreement with the previously reported information about the experimental Ki heterodimer homologs of cruzipain−chagasin (Table 1) and the respective analysis presented in this work, we suggest that the presence of highly specific cross-linkers and chagasin for homologous agonists (cathepsins and cystatins) in humans is a key point of the evolutionary persistence of Chagas disease. Here, CST4 is linked to Chagas disease.