A20: A multifunctional tool for regulating immunity and preventing disease.

A20, also known as TNFAIP3, is a potent regulator of ubiquitin (Ub) dependent signals. A20 prevents multiple human diseases, indicating that the critical functions of this protein are clinically as well as biologically impactful. As revealed by mouse models, cell specific functions of A20 are linked to its ability to regulate diverse signaling pathways. Aberrant expression or functions of A20 in specific cell types underlie divergent disease outcomes. Discernment of A20's biochemical functions and their phenotypic outcomes will contribute to our understanding of how ubiquitination is regulated, how Ub mediated functions can prevent disease, and will pave the way for future therapeutic interventions.