Troponin C2, fast skeletal type (TNNC2)

Troponin C2, fast skeletal type (TNNC2) is a critical calcium-binding protein that serves as the regulatory subunit of the troponin complex in fast-twitch skeletal muscle fibers [4, 11]. It functions as a molecular switch where the binding of calcium ions to its N-terminal EF-hand domains triggers a conformational change in the troponin-tropomyosin complex, exposing myosin-binding sites on actin filaments and initiating muscle contraction [9, 15]. Unlike the cardiac/slow-twitch isoform (TNNC1), TNNC2 is exclusively expressed in fast-twitch skeletal muscle, making it a specific therapeutic target for enhancing muscle strength without affecting cardiac function [13, 16]. Mutations in the TNNC2 gene are linked to congenital myopathies characterized by hypotonia and respiratory weakness [6, 10]. In drug development, TNNC2 is targeted by small-molecule activators like tirasemtiv and reldesemtiv, which sensitize the muscle to calcium to improve physical performance and respiratory capacity in patients with neuromuscular disorders such as amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA) [18, 21, 22].

Other names

Fast skeletal muscle troponin CTroponin C type 2 (fast)fsTnCCFAP85FAP85CMYO15CMYP15MYONRIFast-twitch skeletal muscle troponin C

Fast skeletal muscle troponin activators (FSTAs) bind to the fast skeletal troponin complex and slow the rate of calcium dissociation from the TNNC2 subunit, thereby increasing the calcium sensitivity of the sarcomere and shifting the force-calcium relationship to the left to enhance muscle force production at submaximal stimulation frequencies [8, 12, 16].