The authors, using public datasets, demonstrate that malaria infection, linked to sickle cell disease, induces NLRC5 expression in monocytes, highlighting their critical role in responding to elevated heme levels.1 Monocytes both trigger inflammation to support anti-parasitic immunity in an NLRC5-dependent manner and mediate heme clearance to prevent secondary organ damage. The gene discussed is NLRC5; the disease is sickle cell disease.