MYH1 (myosin heavy chain 1) is a skeletal muscle protein essential for normal hearing through its role in outer hair cell (OHC) function. In the auditory system, MYH1 regulates cochlear amplification by positively modulating prestin (SLC26A5) activity and OHC electromotility 1. MYH1 deficiency in knockout mice results in elevated auditory brainstem response thresholds and absent otoacoustic emissions, reflecting impaired OHC electromotility 1. As a myosin II complex component, MYH1 participates in sarcomeric muscle contraction through actin filament-based motor activity [GO annotations]. In skeletal muscle differentiation, MYH1 expression is modulated during myotube maturation, with reduced MYH1 levels associated with a more oxidative phenotype in IGF1-treated myotubes 2. Biallelic MYH1 variants cause autosomal recessive hearing loss in humans, with variants—particularly in the head domain—abolishing MYH1's prestin-regulatory function and membrane traction force modulation 1. Hearing loss onset ranges from congenital to childhood and is typically non-progressive; three of five affected individuals showed osteopenia 1. A pathogenic E321G mutation in equine MYH1 produces a hyper-contractile phenotype with increased force production and calcium sensitivity 3. MYH1 mutations have also been identified in genetic rhabdomyolysis cases 4.