TCAP (titin-cap/telethonin) is a sarcomeric Z-disc protein essential for muscle assembly and mechanical sensing. Primary Function: TCAP mediates antiparallel assembly of titin molecules at the sarcomeric Z-disc and functions as a mechanosensory component within the titin/Tcap/muscle LIM protein (MLP) complex 1. Mechanism: TCAP interacts with titin, MLP, and calsarcin-1 at the Z-disc, where it tethers calcineurin to transduce mechanical stretch signals during sarcomeric contraction 1. TCAP expression is developmentally regulated and enriched in skeletal and cardiac muscle tissue 2. Disease Relevance: TCAP mutations cause distinct cardiomyopathies and limb-girdle muscular dystrophy (LGMD-2G/LGMD-R7). HCM-associated mutations (T137I, R153H) augment Tcap-titin interactions, while DCM-associated mutations (E132Q, R87Q) impair Z-disc component interactions 1. LGMD-2G represents the predominant TCAP-related phenotype 3, with the c.26_33dupAGGTGTCG mutation being frequent in Asian populations 4. Clinical Significance: TCAP dysfunction compromises sarcomere structural integrity and mechanotransduction, causing progressive muscle weakness and cardiac dysfunction. Recent evidence suggests PXR-mediated TCAP upregulation promotes cardiac recovery post-myocardial infarction 5, offering therapeutic potential for ischemic heart disease.