The critical contribution of the CLR–SYK–CARD9 signaling pathway in human antifungal host defense is clearly portrayed by the observation that CARD9 deficiency is the only— among the >400 known to date—primary immunodeficiency disorder (PID) that promotes fungal-specific infection susceptibility without predisposition to bacterial, viral, or parasitic infections or noninfectious complications. Here, CARD9 is linked to parasitic infectious disease.