Our work in the DNA damage response field was initiated and driven by the desire to understand ataxia-telangiectasia (A-T). A-T is an autosomal recessive disorder initially manifested as ataxia (lack of coordination of movements), usually during the first year of life. This is the early sign of what later becomes a severe, relentlessly progressive, neuromotor dysfunction that renders the patient wheelchair bound toward the end of the first decade of life. The ataxia is a result of progressive degeneration of the cerebellar cortex with striking loss of the Purkinje cells. Telangiectasias (dilated blood vessels) appear later, usually in the eyeballs and sometimes on the ears and face. These are just two features of this multisystem disorder, which also includes immunodeficiency, recurrent respiratory infections in some patients, gonadal and thymic atrophy, genomic instability (manifested as chromosomal breakage and specific translocations), cancer predisposition (mainly lymphoid malignancies), and acute sensitivity to the cytotoxic effect of ionizing radiation (IR) and chemicals that, like IR, induce breaks in the DNA. The gene mutated in these patients, ATM , encodes the ATM protein kinase, which mobilizes the cellular response to double strand breaks in the DNA. ATM phosphorylates numerous substrates that are key players in the various branches of the ATM-mediated network. See “Background” and “Publications” for more about A-T and ATM.