{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nCardiac troponin I, encoded by TNNI3, is the inhibitory subunit of the troponin complex that plays a central role in translating changes in intracellular Ca²⁺ into coordinated myocardial contraction and relaxation. Structural studies have revealed that TNNI3’s protein product is embedded in a highly flexible core domain that, upon Ca²⁺ binding to troponin C, undergoes a conformational change leading to the release of its carboxy‐terminal tail from actin. This process modulates the position of tropomyosin on the thin filament, thereby controlling actomyosin ATPase activity and muscle contractility. In addition, site‐specific phosphorylation and proteolytic processing—such as C-terminal truncation observed during myocardial stunning—further fine-tune its regulatory function. Intriguingly, cardiac-specific kinases (for example, a kinase encoded by TNNI3K) and other interacting proteins (including channels like polycystin-2) have been found to associate directly with troponin I, suggesting that metabolic and signaling pathways converge on TNNI3 to modulate myofilament performance."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMutations in TNNI3 have been directly implicated in diverse cardiomyopathies, including hypertrophic, restrictive, and dilated forms. Functional analyses of missense and deletion mutations demonstrate that many disease-causing variants lead to an increased Ca²⁺ sensitivity of myofilament force generation, diminished inhibitory capacity, or altered binding affinities within the troponin complex. These abnormalities can result in impaired relaxation and diastolic dysfunction, ultimately triggering compensatory hypertrophy or progressive myocardial failure. Systematic genetic screening of families has further underscored the clinical utility of identifying TNNI3 mutations—not only by establishing a molecular diagnosis but also by refining risk stratification in patients with familial cardiomyopathy."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "10", "end_ref": "20"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its mechanistic role in sarcomeric regulation, cardiac troponin I is a critical biomarker of myocardial injury and stress. Sensitive assays have been developed to measure its circulating levels in a variety of clinical settings—including acute coronary syndromes, pulmonary embolism, stroke, and even following strenuous exercise or noncardiac critical illnesses—to aid in diagnosis and prognostication. Altered troponin I release reflects not only myocyte necrosis but may also indicate subclinical contractile dysfunction related to genetic mutations. Meta-analyses of post-interventional release and studies integrating troponin I with clinical risk scores further support its utility in guiding patient management and predicting adverse outcomes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "21", "end_ref": "40"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Soichi Takeda, Atsuko Yamashita, Kayo Maeda, et al. 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Structure and functions."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochemistry (Mosc) (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1134/S0006297913130063"}], "href": "https://doi.org/10.1134/S0006297913130063"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24490734"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24490734"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Vlad Zabrouskov, Ying Ge, Jae Schwartz, et al. 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