The ability to hear, often taken for granted, relies on a remarkably intricate biological process. Now, researchers at Philipps-Universität Marburg in Germany have identified a key protein, dubbed TMEM145, that plays a crucial role in human hearing, specifically in amplifying faint sounds. This discovery, published in the journal Neuron, offers new insights into the mechanics of hearing and potential avenues for treating hearing loss. Understanding the molecular underpinnings of auditory function is a significant step toward addressing a condition that affects millions worldwide.
The research team, led by Professor Dr. Katrin Reimann of the Department of Otorhinolaryngology and Professor Dr. Dominik Oliver from the Institute of Physiology and Pathophysiology, focused on the outer hair cells within the cochlea, the spiral-shaped cavity of the inner ear. These cells aren’t directly responsible for transmitting sound to the brain. instead, they act as biological amplifiers, enhancing the sensitivity of the inner ear to quiet sounds. This amplification is made possible by tiny, hair-like structures called stereocilia, which vibrate in response to sound waves. The team’s work centers on how these stereocilia connect to a structure called the tectorial membrane, which transmits the vibrations.
A Molecular Link in the Chain of Hearing
TMEM145, the protein identified by the Marburg team, forms a ring-like structure at the tips of the stereocilia, essentially organizing and stabilizing the mechanical connection to the tectorial membrane. This connection is vital; without it, the outer hair cells cannot effectively amplify sound. “Our results indicate that TMEM145 functions as a molecular anchoring and organizing center that enables the mechanical stimulation of the hair cells – a prerequisite for the amplifier function of the inner ear to work at all,” explained Professor Reimann. The findings, detailed in the Neuron study, demonstrate that when TMEM145 is absent, the mechanical link is lost.
The research group (from left to right): Paulina Kreye, Katrin Reimann, Dennis Derstroff, Dominik Oliver and Vijay Renigunta.
To demonstrate the protein’s importance, the researchers conducted experiments using genetically modified mice lacking TMEM145. These mice exhibited significant hearing loss and a complete loss of the cochlea’s amplification function. This confirms that TMEM145 is not merely correlated with hearing, but is essential for it.
Implications for Genetic Hearing Loss and Potential Therapies
The discovery of TMEM145’s role has implications for understanding and potentially treating genetic forms of hearing loss. Several other proteins known to be involved in the function of the outer hair cells have already been linked to genetic hearing impairments. TMEM145 now joins this list as a potential candidate gene to investigate in individuals with unexplained hearing loss. Genetic testing could identify mutations in this gene as a cause of auditory dysfunction.
the mouse model suggests a potential “therapeutic window” for intervention. The study indicates that there may be a period of time after the initial disruption of TMEM145 function, before irreversible damage occurs, where treatment could be effective. This opens the door to exploring gene therapy approaches, which are already being investigated for other genetically-caused forms of inner ear deafness. Gene therapy aims to deliver a functional copy of the gene to the affected cells, potentially restoring hearing. However, it’s important to note that these approaches are still under development and require further research.
A Collaborative Approach to Understanding Hearing
The success of this research highlights the importance of interdisciplinary collaboration. The team at Philipps-Universität Marburg brought together expertise from the Clinic for Otorhinolaryngology and the Institute of Physiology and Pathophysiology. This collaboration was further strengthened by an international network of partners, including researchers at Harvard Medical School in Boston and University College London (UCL). “This international cooperation combines different scientific perspectives – from clinical experience to molecular cell biology and genetic models – and makes it possible to comprehensively investigate complex mechanisms of hearing,” said Professor Reimann.
The study was funded by the German Research Foundation (DFG), the British Medical Research Council, and the National Institutes of Health (USA), demonstrating the broad recognition of the importance of this research area. The collaborative effort and funding support underscore the commitment to unraveling the complexities of hearing and developing new treatments for hearing loss.
Original Publication: Dennis Derstoff et al., Neuron (2026), DOI: https://doi.org/10.1016/j.neuron.2026.03.007
Looking ahead, researchers will continue to investigate the precise mechanisms by which TMEM145 functions and explore potential therapeutic strategies targeting this protein. The next step involves further characterizing the protein’s interactions with other molecules within the hair cells to gain a more complete understanding of its role in hearing. The team similarly plans to investigate whether similar proteins exist in humans that could be targeted for therapeutic intervention.
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