Cover Photograph: Superposition of a molecular model of α-actinin on a runner's leg. In humans, the ACTN3 (α-actinin 3) genotype is associated with greater athletic performance, as compared with the ACTN2 phenotype. An ancient family of actin-binding proteins with structural, signalling and metabolic functions, the α-actinins diverged approximately 250–300 million years ago, and ACTN3 has since developed restricted expression in fast muscle fibres. Following gene duplication, the two genes probably diverged in function, explaining why α-actinin-2 cannot completely compensate for the absence of α-actinin-3. See the review by Monkol Lek, Kate G.R. Quinlan and Kathryn N. North in this issue.