Troponin: biology, molecular mechanisms, and multidimensional clinical applications.

Abstract

Troponin is classically recognized as the central regulator of striated muscle contraction. However, emerging evidence indicates that troponin subunits are also expressed in numerous non-muscle cell types, where they perform diverse non-classical functions independent of contractile regulation. Recent studies have implicated troponin in transcriptional regulation, epigenetic remodeling, mitochondrial bioenergetics, and calcium signaling. Troponin has also been shown to inhibit angiogenesis and is present in extracellular vesicles. Together, these findings suggest that troponin participates in fundamental cellular processes that extend far beyond muscle physiology. Despite these advances, the molecular mechanisms underlying these non-classical functions remain incompletely understood, and the relationship between troponin's structural biology and its roles in both cancerous and non-cancerous cells has been only partially explored. In this review, we integrate current experimental evidence with recent bioinformatic analyses to provide a comprehensive overview of troponin biology beyond the sarcomere. Particular emphasis is placed on the molecular mechanisms governing nuclear localization, protein-protein interactions, transcriptional and epigenetic regulation, and mitochondrial function, as well as on the distinct biological roles of individual troponin isoforms. We further discuss the growing evidence linking aberrant troponin expression and function to cancer biology, highlighting its context- and isoform-dependent activities that may either promote or suppress tumor development. Collectively, these findings redefine troponin as a multifunctional regulatory protein and identify it as a promising subject for future research.