MYL2 encodes myosin light chain 2, a contractile protein essential for cardiac muscle function and development. MYL2 is one of eight genes with definitive evidence for causing hypertrophic cardiomyopathy (HCM), representing a well-established sarcomere gene 1. In genetic screening studies, MYL2 mutations account for approximately 2-3% of HCM cases, making it one of the less common but clinically significant causative genes 234. The protein plays a crucial role in cardiac contractility through regulation of cross-bridge cycling kinetics and myosin head dynamics. Systematic genetic screening approaches recommend analyzing MYL2 as part of the core panel following the two major genes MYBPC3 and MYH7 3. Penetrance studies show that sarcomere protein mutation carriers, including those with MYL2 variants, have approximately 50% risk of developing HCM over 15 years of follow-up 4. Recent studies have identified both pathogenic variants and variants of uncertain significance in MYL2 among HCM patients, with some classified as likely pathogenic based on familial segregation analysis 56. The gene's involvement in cardiac development and contractile function makes it clinically relevant for genetic counseling and family screening in HCM.