In this review, we describe the PI3K/AKT/mTOR/S6K signaling cascade, focusing on the genetic and molecular defects of the different “immune TOR-opathies,” and on the impact of this pivotal pathway in the development of immune deficiency and immune dysregulation, a hallmark of “immune TOR-opathies.” The gene discussed is RPS6KB1; the disease is Immunodeficiency.