Regulation of Tmem30b-Mediated Apical Membrane Homeostasis in Auditory Outer Hair Cells Is Critical for Hearing

    April 2026 in “ Proceedings of the National Academy of Sciences ”
    Miao Chang, Guodong Hong, Shan Gao, Cheng Cheng, Jia Yuan, Yu Xiao, Ruifeng Qiao, Jing Ke, Xinhao Wu, Tiancheng Zhang, Guo S, Runze Jiang, Ziyi Liu, Jing Zhou, Xiaohan Zhang, Yunhao Wu, Xiaoxu Zhao, Wenhua Li, Shuyuan Shen, Zuhong He, Xiuli Bi, R J Chai, Xiaolong Fu
    TLDR Tmem30b is essential for hearing by maintaining hair cell structure in the ear.
    The study identifies Tmem30b as a crucial regulator of membrane lipid homeostasis in auditory outer hair cells (OHCs), essential for hearing. Tmem30b, a phospholipid-flippase chaperone, forms a complex with Atp8b1 to maintain phospholipid asymmetry in OHCs. Disruption of this complex leads to stereocilia degeneration and hearing loss. The research demonstrates that AAV-mediated delivery of Tmem30b can alleviate stereocilia defects in Tmem30b−/− and Atp8b1−/− mice, and overexpression of Tmem30b in hair cells protects against noise-induced and aminoglycoside-induced hearing loss. These findings suggest that targeting Tmem30b–Atp8b1-mediated lipid regulation could be a therapeutic strategy for preventing hearing loss.
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