SUMOylation of proteins is described in the early stages of viral infections that leads to the polyubiquitination of cytosolic receptors such as retinoic acid-inducible receptor gene I (RIG-I) and melanoma differentiation-associated protein 5 (MDA5), preventing their degradation through the ubiquitin–proteasomal system [55,56]. The gene discussed is RIGI; the disease is viral infectious disease.