Lmod2, or Leiomodin-2, is an actin-binding protein and a key regulator of thin-filament length in muscles [2,3,4,5,7,8]. It promotes the elongation of actin filaments through polymerization at pointed ends, which is crucial for the normal assembly of striated muscle thin filaments and is essential for life [2].

In mice, knockout (KO) of Lmod2 leads to abnormally short thin filaments in the heart, resulting in dilated cardiomyopathy (DCM), ventricular arrhythmias, and postnatal or juvenile lethality [3,4,7]. Conditional knockout (CKO) in skeletal muscle shows decreased force production in both fast-and slow-twitch muscles. In slow-twitch soleus muscle, there are shorter thin filaments, increased Lmod3 levels, and a myosin fiber type switch [1]. In human patients, biallelic variants in LMOD2 are associated with DCM, often presenting in neonates or infants [2,3,6].

In conclusion, Lmod2 is essential for the integrity of sarcomeres and intercalated discs in the heart and for effective skeletal muscle contraction. Studies using Lmod2 KO and CKO mouse models have significantly advanced our understanding of its role in DCM, highlighting its importance in the pathogenesis of this cardiac disease [1,3,4,7].