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Chagas disease, caused by <i>Trypanosoma cruzi</i> infections, is included in the group of neglected diseases, and efforts to develop new therapeutic or immunoprevention approaches have not been successful. After the publication of the <i>T. cruzi</i> genome, the number of molecular and biochemical studies on this parasite has increased considerably, many of which are focused on families of variant surface proteins, especially trans-sialidases, mucins, and mucin-associated proteins. The disperse gene protein 1 family (DGF-1) is one of the most abundant families in the <i>T. cruzi</i> genome; however, the large gene size, high copy numbers, and low antibody titers detected in infected humans make it an unattractive study target. However, here we argue that given the ubiquitous presence in all <i>T. cruzi</i> species, and physicochemical characteristics, the DGF-1 gene family may play and important role in host-parasite interactions.