MYOM2 (myomesin 2) is a major structural component of the myofibrillar M-band in the sarcomere, where it functions as a hub gene binding myosin, titin, and light meromyosin in a dose-dependent manner 1. The gene is transcriptionally regulated by the SIM2/ARNT1 heterodimer complex through a non-canonical E-box sequence 2. MYOM2 mutations are associated with congenital and acquired cardiac diseases. Patient-derived cardiomyocytes carrying MYOM2 mutations exhibit myofibrillar disarray and reduced passive force generation 1. Disease models demonstrate that MYOM2 loss-of-function causes diastolic dysfunction, cardiac arrhythmias, and increased oxidative stress 3, while animal studies reveal synergistic genetic interactions between MYOM2 and other sarcomere genes 1. MYOM2 has been identified as a candidate gene for hypertrophic cardiomyopathy and Tetralogy of Fallot 1. Plasma MYOM2 levels serve as a biomarker for muscle disease severity. In oculopharyngeal muscular dystrophy, circulating MYOM2 protein levels are elevated over 200% in patients with limb weakness and correlate strongly with muscle fatty infiltration 4. Additionally, MYOM2 reduction in plasma represents a biomarker of dystrophin restoration in Duchenne muscular dystrophy treatment response 5. MYOM2 expression is upregulated in extraocular muscles exhibiting primary inferior oblique overaction 6.