Editorial Some rat: A very special rat with a rather special titin Cycling cross-bridges, the molecular interactions between the contractile proteins actin and myosin, generate the muscle force that underlies cardiac pressure development. In striated muscle, these proteins are organized in the thick and thin filaments that together form the sarcomere. A more recent discovery localizes a third filament to the sarcomere, one that is composed of titin. Titin, also known as connectin, is a giant protein (3–4 MDa) that is an abundant protein in striated muscle forming up to 10% of the total protein content of the cardiac cell. Titin extends half the length of the sarcomere from the Z-disc through the I-band and A-band on to the M-line (~1 μm). The molecule is tightly anchored at its NH 2-terminus in the Z-disk via interactions with alpha-actinin and at its C-terminal domain to the M-line via interactions with myosin. The cell biology of titin has been the subject of intense study by several groups following its discovery in the seventies [1,20]. It was immediately recognized that a significant function of titin in the sarcomere might be structural. Indeed, titin has emerged as the main cellular structure responsible for passive striated muscle cell stiffness [2,3]. Furthermore, within the physiological range of cardiac volume, titin appears to be responsible for a significant portion of the diastolic passive filling pressure of the heart; the remainder of the elastic force being generated by extra-cellular matrix collagen [4]. The elasticity of titin originates within the I-band portion due to the presence of i) tandem immunoglobulin (Ig) repeats, ii) a region rich in proline (P), glutamate (E), valine (V), and lysine (K), the PEVK region and iii) a region with a sequence unique to cardiac titin, the N2B region. Alternative splicing provides additional tandem Ig repeats that insert between the N2B and PEVK regions. These longer titin isoforms also have an N2A region and are termed N2BA. In a sarcomere at slack length, titin is highly folded with many of the regions acting as entropic springs. As the sarcomere is stretched, the links between the tandem Ig repeats extend first, followed by PEVK unfolding and finally N2B region unfolding at the upper end of the physiological range of sarcomere lengths. The tandem Ig repeats are thought to unfold only beyond the non physiological range of sarcomere lengths and forces [2,3]. It has become increasingly clear recently that titin's functions are far more complex and that this giant molecule may play a much larger role in striated muscle physiology than merely as a passive stress bearing protein. For example, it has been suggested that titin plays an important role in regulating both protein turnover and gene expression in response to mechanical strain [2,3]. Moreover, the protein itself is a kinase capable, at least in-vitro, of phosphorylating telethonin (T-cap), a titin capping protein located at the Z-disk region of titin. However, whether this actually occurs in vivo is not clear since titin's kinase domain is physically far removed from the T-cap substrate.