N2B

N2B refers to a cardiac titin isoform region, part of the giant sarcomeric protein titin encoded by the TTN gene. Titin spans half of the sarcomere and contains an elastic I-band segment that functions as a molecular spring. The N2B element is a specific exon-encoded region within this I-band and represents one of the two principal adult cardiac isoforms of titin, the other being N2BA. In adult human ventricles, both isoforms are expressed, with N2B being the shorter form and contributing to higher passive stiffness of the myocardium relative to the longer N2BA isoform.

The N2B region contributes to the passive elastic properties that influence diastolic filling. Its relative contribution to stiffness is affected by alternative splicing, which shifts the N2B:N2BA ratio during development and in disease, thereby altering myocardial compliance. Post-translational modifications also modulate titin’s elasticity: phosphorylation by kinases associated with cAMP and cGMP signaling can reduce titin-based passive tension, increasing ventricular compliance.

Clinical relevance is primarily tied to titin’s broader role in cardiac function. Mutations in TTN, including truncating variants, are a common cause of dilated cardiomyopathy and can affect titin’s mechanical properties. While the N2B element itself is studied as part of titin’s regulatory spring, its impact on heart function is understood within the context of isoform expression and post-translational regulation that determine overall myocardial stiffness and diastolic performance.