Knock-in mice expressing UBA domain-mutant cIAP1 are more sensitive to TNF-mediated systemic inflammatory response syndrome (SIRS), implying that UBA domain-mediated RIPK1 K48-linked ubiquitination is an important step in modulating the cytotoxic potential of the TNF-mediated response. The gene discussed is RIPK1; the disease is systemic inflammatory response syndrome.