Ataxia-Telangiectasia (A-T) is an autosomal recessive disorder which presents a wide array of clinical symptoms including enhanced cancer predisposition and progressive cerebellar degeneration leading to general neuromotor dysfunction. The A-T cellular phenotype consists of higher levels of chromosome breakage, increased sensitivity to ionizing radiation and radiomimetic drugs, and defective cell cycle checkpoints in response to genome damage. Positional-cloning of the gene mutated in A-T, designated ATM, identified a 13 kb transcript encoding a 3056 amino acid protein which possesses a carboxy-terminal domain with distinct homology to phosphatidylinositol-3 kinase. Furthermore, ATM related proteins have been identified in yeast, Drosophila and other mammalian species which are involved in cell cycle control and cellular responses to DNA damage. Development of cellular and animal models for A-T can serve to better dissect the role and involvement of ATM in cell cycle regulation, cancer development, neuronal cell death and other hallmark symptoms of this disorder.