Myosin light chain, phosphorylatable, fast skeletal muscle (MYLPF)

Myosin light chain, phosphorylatable, fast skeletal muscle (MYLPF), also known as MLC2, is a regulatory subunit of the fast skeletal muscle myosin complex. It plays a critical role in modulating muscle contraction by regulating the ATPase activity of the myosin heavy chain and increasing the sensitivity of the contractile apparatus to calcium through phosphorylation by myosin light chain kinase (MLCK) (UniProt Q96A32). In fast-twitch fibers, MYLPF phosphorylation is a key mechanism for post-tetanic potentiation, enhancing force production during repetitive stimulation (PubMed: 26942284). Mutations in the MYLPF gene are linked to Distal Arthrogryposis, a group of disorders characterized by joint contractures, highlighting its essential role in normal musculoskeletal development and function (NCBI Gene: 29895). While most clinical focus in myosin modulation has targeted cardiac isoforms, fast skeletal myosin activators (FSMAs) are being explored to treat neuromuscular diseases and muscle wasting conditions by increasing the efficiency of the power stroke (Cytokinetics). Experimental compounds like CK-2066260 demonstrate the potential to selectively target fast skeletal myosin to improve physical function in patients with spinal muscular atrophy or ALS. These drugs aim to stabilize the pre-powerstroke state or accelerate the transition to the force-generating state, thereby boosting muscle performance. However, therapeutic development faces challenges such as ensuring selectivity over cardiac and smooth muscle isoforms to avoid systemic toxicity.

Other names

MLC2MLC-2DTNB-light chainMyosin light chain 2, skeletal muscle isoformHUMMLC2B

Direct modulation of the myosin motor domain to enhance or inhibit cross-bridge cycling and calcium sensitivity in fast-twitch muscle fibers.