Myo6, a member of the myosin family, is a unique actin-based motor protein that moves cargo towards the minus ends of actin filaments. It is crucial in multiple biological processes, with its loss or overexpression in humans linked to various pathologies like deafness, cardiomyopathy, neurodegenerative diseases, and cancer. Myo6 interacts with numerous binding partners to mediate distinct functions along the endocytic pathway, and also plays a role in regulating the actin and septin cytoskeleton [1].

In a Myo6WT/C442Y mouse model, AAV-PHP.eB vector-mediated in vivo delivery of Staphylococcus aureus Cas9-single-guide RNA complexes was used to edit the Myo6 gene. The editing rescued auditory function up to 5 months post-injection, as evidenced by improvements in auditory brainstem response, distortion product otoacoustic emission thresholds, cell survival, hair bundle morphology, and calcium levels [2].

In a Myo6 knockout background in a collagen-induced arthritis (CIA) mouse model, MYO6 deficiency attenuated arthritis development and bone destruction, and impaired osteoclast differentiation by inhibiting NFATc1 induction. MYO6 was shown to be essential for podosome organization and endosome transportation in osteoclasts [3].

In conclusion, Myo6 is vital for auditory and vestibular function, and also plays a role in osteoclast-mediated joint damage. Gene editing and knockout mouse models have been instrumental in revealing these functions, providing insights into potential therapeutic strategies for hearing loss and arthritis-related diseases.