MYO3A

MYO3A (myosin IIIA) is an unconventional actin-dependent motor protein of the class III myosin family that contains an N-terminal kinase domain and is highly expressed in the retina and cochlea, indicating specialized functions in sensory cells^[1]. Mechanistically, MYO3A regulates actin-rich protrusions and stereocilia-associated structures through its motor and tail domains, including a unique tail homology II (THD2) actin-binding region that distinguishes it from many other myosin classes^[2]. Evidence further indicates that MYO3A participates in the transport of protocadherin-15, a key component of the mechano-electrical transduction complex in stereocilia, linking the protein to sensory signal processing in inner-ear hair cells^[2]. In disease contexts, pathogenic MYO3A variants cause autosomal recessive and autosomal dominant nonsyndromic hearing loss, and affected individuals typically develop progressive sensorineural hearing impairment that can worsen over time^[3][4]. Experimental studies have also shown that mouse models carrying human MYO3A mutations develop hearing loss that initially affects high frequencies and subsequently extends across the auditory spectrum, supporting a direct role in auditory function and disease mechanisms^[2]. Compared with the related isoform MYO3B, MYO3A is more efficient at promoting the formation and elongation of stable actin-based protrusions, highlighting functional specialization within class III myosins and providing a useful framework for mechanistic studies of stereocilia biology and hearing-loss pathogenesis^[1].