A family of proteins, Homers 1, 2 and 3, involved in activity-dependent control of signal transduction has been recently described in neurons [Xiao, B., Tu, C. J., Petralia, R. S., Yuan, J. P., Dean, A., Breder, C. D., Ruggiero, A., Lanahan, A. A., Wenthold, R. J., and Worley, P. F. (1998) Homer regulates the association of group 1 metabotropic glutamate receptors with multivalent complexes of Homer-related, synaptic proteins. Neuron 21, 107-716]. By RT-PCR and RNasePA, mRNAs transcripts for Homer la and Homer 1c, but not Homer 1b, are detected in both skeletal and cardiac muscles of the rat. Full-length cloning of Homer 1a and Homer 1c cDNAs has been accomplished: There is no tissue specificity, by comparing skeletal muscle, cardiac muscle and cerebellum, and there are a few species-specific base substitutions, by comparing rat and mouse sequences. The regulatory mechanism exerted via transition of Homer 1 isoform composition may be operative in striated muscles.