While these studies have placed the spotlight on the role of TLR4 in the pathogenesis of NEC, the observation that most premature infants do not develop NEC despite the seemingly tonic activation of TLR4 within the intestinal epithelium and elsewhere raises the important possibility that TLR4 signaling must somehow be curtailed within the newborn intestinal epithelium, in order to limit the propensity for spontaneous NEC development. The gene discussed is TLR4; the disease is necrotizing enterocolitis.