CARD9 is a critical antifungal molecule yet there remain significant gaps in our understanding, including the organ-specific functions operating in the skin, mucosal surfaces, and deep tissues, why CARD9-deficiency doesn't predispose to more infections by other fungal organisms, and how some CARD9-deficient patients can live for 2 or 3 decades before developing any serious fungal infections while others with identical mutations develop severe fungal disease early in life. The gene discussed is CARD9; the disease is fungal infectious disease.