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

The study identifies Tmem30b as a crucial regulator in outer hair cells (OHCs) for hearing, highlighting its role in maintaining the structure of hair bundles in the cochlea. Tmem30b, a phospholipid-flippase chaperone, initially localizes to the nuclear membrane and later stabilizes in the stereocilia and cuticular plate. Tmem30b −/− mice show early-onset hearing loss due to disorganized OHC stereocilia, starting at P7. Tmem30b partners with Atp8b1 to regulate phospholipid asymmetry, and disruption of this complex destabilizes OHC bundles. AAV-mediated delivery of Tmem30b to hair cells corrects stereocilia defects in Tmem30b −/− and Atp8b1 −/− mice, and overexpression of Tmem30b protects against noise-induced and aminoglycoside-induced hearing loss. The findings suggest Tmem30b–Atp8b1–mediated lipid regulation as a potential therapeutic target for hearing loss.