Abstract:Protein ubiquitylation is a post-translational modification that existed widely in eukaryotic cells. This phenomenon was initially described in the studies of the mechanism of cytosol protein degradation. There is increasing evidence that both ubiquitination and its reversal process， deubiquitination， play crucial roles in innate and adaptive immune response by regulating the function of the different immune cells， consequently controlling occurrence and development of a variety of human diseases， including autoimmune diseases， infectious diseases and malignant tumors. In this review， we focus on the latest research progresses on the role of ubiquitylation in the regulation of immune cell function and the development of multiple human diseases.