MYO6 (myosin VI) encodes an unconventional actin-based motor protein that uniquely moves toward the minus-end of actin filaments, distinguishing it from other myosins 1. The protein functions in multiple cellular processes including vesicular membrane trafficking, endocytosis, and autophagy 2. MYO6 mediates clathrin-mediated endocytosis in epithelial cells and, together with TOM1, delivers endocytic cargo to autophagosomes, promoting autophagosome maturation and lysosomal fusion 2. The protein exhibits precise spatiotemporal regulation through an auto-inhibited off-state that can be released by specific binding partners like GIPC1, which also triggers proximal dimerization essential for proper function 3. In cancer cells, MYO6 bridges GSDME and endocytic adaptor AP2, mediating endolysosomal degradation that can be enhanced by the metabolite spermidine 4. Pathogenic variants in MYO6 cause autosomal dominant (DFNA22) and recessive (DFNB37) forms of hearing loss, with variants contributing to both early-onset deafness and severe age-related hearing loss 51. Gene therapy approaches using CRISPR-Cas9 systems have shown promise in rescuing auditory function in mouse models 6, making MYO6 a candidate for future hearing loss treatments 7.