The Giant Protein Titin: A Major Player in Myocardial Mechanics, Signaling, and Disease

Henk L. Granzier, Siegfried Labeit

Research output: Contribution to journalReview articlepeer-review

452 Scopus citations


The sarcomere contains, in addition to thin and thick filaments, a filament composed of the giant protein titin (also known as connectin). Titin molecules anchor in the Z-disc and extend to the M-line region of the sarcomere. The majority of titin's I-band region functions as a molecular spring. This spring maintains the precise structural arrangement of thick and thin filaments, and gives rise to passive muscle stiffness; an important determinant of diastolic filling. Earlier work on titin has been reviewed before. In this study, our main focus is on recent findings vis-à-vis titin's molecular spring segments in cardiac titins, including the discovery of fetal cardiac isoforms with novel spring elements. We also discuss new insights regarding the role of titin as a biomechanical sensor and signaling molecule. We will end with focusing on the rapidly growing knowledge regarding titinopathies.

Original languageEnglish (US)
Pages (from-to)284-295
Number of pages12
JournalCirculation research
Issue number3
StatePublished - Feb 20 2004


  • Connectin
  • Contractility
  • Myocardial stiffness
  • Passive stiffness
  • Stretch

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine


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