MALT1 encoding a caspase-like cysteine protease is a central signaling component in innate and adaptive immunity by regulating NF-κB and other key signaling pathways in different cell types. MALT1 has a T-cell intrinsic role in regulating the homeostasis and function of thymic and peripheral T cells. Patients with homozygous missense mutation in MALT1 have severely impaired T-cell proliferation to antigens and antibody responses to vaccination-defective nuclear factor-κB activation and IL-2 production resulting in combined immunodeficiency. This evidence concerns the gene CTSB and immunodeficiency disease.