Guillamot et al. revealed a critical role for mouse SPOP in restricting inflammation by targeting MyD88 for degradation [29], and a parallel study by Jin et al. has shown that the human SPOP ubiquitin ligase complex suppresses the growth of diffuse large B-cell lymphoma by negatively regulating MyD88/NF-κB signaling [35]. The gene discussed is SPOP; the disease is diffuse large B-cell lymphoma.