BTK and Bruton-type agammaglobulinemia: X-linked (Bruton’s) agammaglobulinemia, as one of the very first detected primary immunodeficiencies was described in 1952 [22]; the discovery of the corresponding gene happened approximately 40 years later, leading to deep molecular insight into the role of BTK in B cell commitment [23]; however studies on ITK deficiency in mice and in vitro were conducted long before the first patient was discovered in 2009.