The efficacy of IL-1 biologics in clinic for the treatment of auto-inflammatory disorders, including CAPS, provides a strong rationale for focusing on IL-1 pathway and leveraging the availability of Il-1 receptor (Il-1r) null mice to determine the role of this cytokine in NLRP3-induced skeletal manifestations. The gene discussed is NLRP3; the disease is cryopyrin-associated periodic syndrome.