ACTA1 encodes skeletal muscle alpha-actin, the predominant actin isoform in sarcomeric thin filaments of adult skeletal muscle 1. It is essential for muscle contraction, functioning alongside myosin to generate myofibrillar force 12. ACTA1 mutations represent a major genetic cause of congenital myopathies, with 447 pathogenic/likely pathogenic variants now identified 3. The vast majority (74%) of variants cause nemaline myopathy, characterized by diagnostic nemaline rods in muscle fibers 34. ACTA1 mutations also produce five overlapping histopathological phenotypes including intranuclear rod myopathy, actin filament aggregates, congenital fiber-type disproportion, and core-like areas 1. Clinical phenotypes have expanded to 20 distinct presentations, with emerging cardiomyopathy phenotypes 35. Most mutations are dominant and de novo; only 10% are recessive genetic or functional nulls 1. Disease is frequently severe, with many patients experiencing rapid progression and early mortality 16. Genotype-position correlations help predict prognosis 4. Currently, only supportive treatment is available, though preclinical therapeutic strategies are under investigation 32.