Tropomyosins are a family of actin binding proteins encoded by a group of highly conserved genes. Humans have four tropomyosin-encoding genes: TPM1, TPM2, TPM3, and TPM4, each of which is known to generate multiple isoforms by alternative splicing. promoters, and 3' end processing. TPM1 is the most versatile and encodes a variety of tissue specific isoforms. The TPM1 isoform specific to striated muscle, designated TPM1alpha, consists of 10 exons: 1a, 2b, 3, 4, 5 6b, 7, 8, and 9a/b. In this study, Using RT-PCR with adult and fetal human RNAs, we present evidence for the expression of a novel isoform of the TPM1 gene that is specifically expressed in cardiac tissues. The new isoform is designated TPM1kappa and contains exon 2a instead of 2b. Ectopic expression of human GFP.TPM1kappa fusion protein can promote myofibrillogenesis in cardiac mutant axolotl hearts that are lacking in tropomyosin. (C) 2004 Elsevier Inc. All rights reserved.