One of the steps in the evolution of tetrapod limbs was the loss of the distinctive fringe of fin rays and fin folds found in the fins of fishes. It is now shown that two novel proteins, actinodin 1 and 2, are essential structural components of fin rays and fin folds in zebrafish, and are also encoded in the genomes of other teleost fish and at least one species of shark, but not in tetrapods. It is suggested that the loss of these genes may have contributed to the fin-to-limb transition in tetrapod evolution.