Fast skeletal muscle troponin T (fTnT) is a protein that in humans is encoded by the TNNT3 gene. The TNNT3 gene is located at 11p15.5 in the human genome, encoding the fast skeletal muscle isoform of troponin T (fsTnT). fsTnT is an ~31-kDa protein consisting of 268 amino acids including the first methionine with an isoelectric point (pI) of 6.21 (embryonic form). fsTnT is the tropomyosin-binding and thin filament anchoring subunit of the troponin complex in the sarcomeres of fast twitch skeletal muscle. TNNT3 gene is specifically expressed in vertebrate fast twitch skeletal muscles. Evolution TNNT3 gene evolved as one of the three TnT isoform genes in vertebrates. Each of the TnT isoform genes is linked to an upstream troponin I (TnI, one of the other two subunits of the troponin complex) isoform gene, and fsTnT is linked with fsTnI genes (Fig. 1). Sequence homology and protein epitope allosteric similarity data suggest that TnT gene was originated by duplication of a TnI-like ancestor gene and fsTnT was the first TnT emerged. Whereas significantly diverged from the slow skeletal muscle TnT (ssTnT encoded by TNNT1) and cardiac TnT (cTnT encoded by TNNT2), Structure of fsTnT is conserved among vertebrate species (Fig. 2), reflecting specialized functional features of the different muscle fiber types. Alternative splicing Mammalian TNNT3 gene contains 19 exons. Alternative RNA splicing of 8 of them significantly increases structural variations of fsTnT. Two variable regions of the fsTnT protein are generated by alternative splicing (Fig. 3). In the N-terminal region of fsTnT, exons 4, 5, 6, 7 and 8 are alternatively spliced in adult skeletal muscle cells. A fetal fsTnT exon located between exons 8 and 9 is specifically expressed in embryonic muscle (Briggs and Schachat 1993). Exons 16 and 17, previously designated as α and β exons, in the C-terminal region of fsTnT are alternatively spliced in a mutually exclusive manner. Avian Tnnt3 gene has evolved with additional alternatively spliced exons, w, P1-7(x) and y, encoding the N-terminal variable region (Fig. 3). Reflecting the power of combined alternative splicing of multiple exons to generate fsTnT variants, two-dimensional gel electrophoresis detected more than 40 different fsTnT splice forms in chicken leg muscle. Developmental regulation Through alternative splicing of the fetal exon and other alternative exons in the N-terminal variable region, the expression of fsTnT during mammalian and avian development undergoes a high molecular to low molecular weight isoform switch in