Investigating a single immunoglobulin interleukin-1–related receptor (SIGIRR) mutation identified in an infant with necrotizing enterocolitis reveals that signal transducer and activator of transcription 3 (STAT3)–microRNA–mediated repression of interleukin-1–related associated kinase 1(IRAK1) protein is lost with SIGIRR mutation. The gene discussed is STAT3; the disease is necrotizing enterocolitis.