Titin, the biggest single (poly) peptide found in humans, and throughout nature 
so far, was long considered as a good candidate for inherited muscle diseases. 
However, disease-causing defects were not known until recently, when this 
central sarcomeric protein was associated with human skeletal tibial muscular 
dystrophy (TMD/LGMD2J), dilated cardiomyopathy (DCM) and hypertrophic 
cardiomyopathy (HCM). Several mutations in different parts of titin have now 
been identified and more are expected. Spontaneous mouse and zebrafish mutants 
have also been reported. Experimental knock-outs are not viable, even in cases 
where just a c-terminal part of the gene was silenced, telling something of the 
basic importance of titin for life. In this article we review the current known 
structure and functions of this elementary molecule with some emphasis on the 
only defects so far known to cause human skeletal muscle disease, mutations in 
the c-terminal M-line part of titin.