TNNC2 encodes fast skeletal muscle troponin C, a critical calcium-binding regulatory protein of the troponin complex essential for striated muscle contraction 1. As a component of the troponin regulatory unit, TNNC2 binds calcium ions to relieve the inhibitory action of troponin I on actin filaments, enabling muscle force generation 2. Pathogenic variants in TNNC2 cause congenital myopathy 15, a dominantly inherited muscle disease characterized by impaired force response to calcium 2. Mechanistically, disease-causing variants disrupt calcium and troponin I binding sites, severely reducing sarcomeric force generation in response to calcium 2. Notably, the fast skeletal muscle troponin activator tirasemtiv successfully restored contractile function in patient myofibers, demonstrating therapeutic potential 2. Beyond its primary skeletal muscle function, TNNC2 expression appears dysregulated in several malignancies including head and neck squamous cell carcinoma and prostate cancer, where it has been identified as a potential biomarker associated with prognosis 34. Additionally, TNNC2 participates in calcium signaling pathways implicated in sex-associated differences in ankylosing spondylitis 5. These findings establish TNNC2 as fundamental to normal skeletal muscle contractility and highlight its relevance to both congenital myopathies and disease progression in non-muscular tissues.