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Humans, like all animals, depend on sensory systems to perceive different aspects of the physical world. One of the most remarkable achievements of evolution has been the development of sensory cells that are specialized to detect unique aspects of this world such as a single photon or a single molecular odorant. Similarly, our ability to perceive sound is mediated through the vibration of exquisitely sensitive stereociliary bundles located on the luminal surfaces of mechanosensory hair cells. A deflection of a little as 1 nM at the tip of the stereociliary bundle is sufficient to elicit a change in the resting potential and synaptic activity of the cell (1). Unraveling the molecular mechanisms that mediate the perception of physical stimuli has been one of the most exciting and rewarding endeavors in modern biology. The characterization of the phototransduction cascade has not only provided insights into the function of the visual system but also contributed profoundly to our understanding of G protein-coupled receptor signaling (2). Surely similar insights regarding mechanotransduction will be obtained once the molecular pathways underlying this sensory modality have been revealed. However, the limited number of mechanosensory hair cells present in any single organism has impeded our ability to dissect the molecular basis of mechanotransduction. Although ≈30 million photoreceptors can be obtained from a single rodent retina, both cochleae from the same animal contain <20,000 mechanosensory hair cells (3, 4). The relative scarcity of these cells emphasizes not only their exceptional level of efficiency but also another daunting aspect of inner ear biology: In mammals, mechanosensory hair cells are generated only during embryogenesis. Over time, and with marked influences from environment and genetic makeup, mechanosensory hair cells are …

Has hair cell loss MET its match?