Aberrant activation of the NLRC4 inflammasome was recently identified in de novo gain-of-function (GOF) mutations in NLRC4 in the context of macrophage activation syndrome (MAS), neonatal enterocolitis, fetal thrombotic vasculopathy, familial cold autoinflammatory syndrome and even death [4] but reports are scarce with only 12 cases identified in the literature. The gene discussed is NLRC4; the disease is macrophage activation syndrome.