The human body is a marvellously well-tuned machine and, as illustrated throughout this issue, mistakes can be costly. Indeed, one small error in a protein can have devastating consequences for the organism.

Ataxia-telangiectasia is a rare progressive neurological disorder that results from mutations in the ATM kinase. One function of this protein is in repairing double-strand DNA breaks, and a Highlight on page 166 reports how neurons with damaged DNA survive — and subsequently malfunction — in the absence of ATM. If this appetizer has left you craving more knowledge on ATM, turn to the Review by Michael Kastan and Dae-sik Lim on page 179, about the many substrates and functions of this protein.

Alzheimer's disease is another, more common, neurodegenerative disease that is characterized by the deposition of insoluble amyloid plaques. As described in the Review by Harald Steiner and Christian Haass on page 217, these plaques may accumulate due to defects in the presenilins, proteases that process the β-amyloid precursor protein.

Mutations in single proteins can also affect various other organs. Take, for example, the many skin blistering diseases caused by mutations in cytoskeletal proteins. Kathy Green and Claire Gaudry describe in a Review on page 208 why desmosomal proteins are important for the integrity of the skin.

Finally, cancers can result from mutations in individual proteins, although more than one defect is usually necessary to cause disease. The Review by Annie Yang and Frank McKeon on page 199 tells you about the guardian of the genome's big brothers, p63 and p73. These two-faced proteins can both aid and obstruct the tumour-suppressor activity of p53.