Functional studies in primary human cells from CNO/CRMO patients and in genetically modified THP-1 monocytes carrying the index-case P2RX7 variant c.349C > T/p.Arg117Trp/rs28360445 confirmed increased inflammasome assembly and associated pro-inflammatory cytokine release (namely IL–1β and especially IL–18) that was, however, accompanied by reduced pyroptosis. The gene discussed is IL1B; the disease is chronic recurrent multifocal osteomyelitis.