Titin is the largest protein in mammals; it forms an elastic filament along the 
myofibril of cardiac and skeletal muscles. Novel studies employing the recently 
available varied technologies have revealed the molecular mechanisms by which 
titin generates passive force in the sarcomere in response to external stretch. 
Changes in titin stiffness occur during heart disease via a shift in the 
expression ratio of the two main titin isoforms, called N2B (stiff type) and 
N2BA (compliant type) titins. Protein kinase (PK)A, PKG and PKC phosphorylate 
the cardiac specific I-band titin segment, resulting in an acute decrease (by 
PKA and PKG) or increase (by PKC) in passive force. It has also been discovered 
that titin performs roles that go beyond passive force generation, by enhancing 
or terminating active force production, thereby adjusting the Frank-Starling 
mechanism of the heart. Therefore, titin is a self-adjustable and 
multi-functional spring that is indispensable for proper heart functions. Here, 
we discuss how titin regulates the passive and active properties of cardiac 
muscle in normal physiological conditions as well as in chronic heart disease.