National Institutes of Health scientists have uncovered a hidden function in proteins long linked to hearing: they shuttle fatty molecules across cell membranes in inner ear hair cells. Disruptions to this process from genetic flaws, noise damage or medications destroy the cells, leading to irreversible deafness, according to findings presented at the 70th Biophysical Society Annual Meeting in San Francisco from February 21-25, 2026.

Inner ear hair cells transform sound vibrations into electrical signals for the brain. Tiny stereocilia bundles on these cells bend with sound waves. That motion opens ion channels, sparking the neural response.

Hubert Lee, a postdoctoral fellow in Angela Ballesteros’s lab at the National Institute on Deafness and Other Communication Disorders, described the process. “Sound vibrations bend these hair-like structures,” Lee said. “It opens channels that let ions flow into the cell, triggering a signal that carries sound to the brain.” Problems with the channel proteins kill hair cells. Those cells do not regenerate. Hearing loss follows permanently.

The proteins, TMC1 and TMC2, form those channels. Mutations in TMC1 rank among top causes of inherited deafness. The NIDCD team revealed a second role for them: acting as lipid scramblases. These molecular machines flip phospholipids—fatty membrane components—from one side of the cell barrier to the other.

Cells maintain strict phospholipid order across their membranes. Phosphatidylserine stays inside normally. When it flips outward, it signals cell death, known as apoptosis. Ballesteros’s group found mouse hair cells with deafness-causing TMC1 mutations show this flip. Membranes bleb and disintegrate.

“Hair cells from mouse models carrying mutations in TMC1 that cause hearing loss exhibit this membrane dysregulation,” Ballesteros said. “Phosphatidylserine gets externalized, and the membrane starts blebbing and falling apart. This is an apoptotic hallmark. It’s what’s killing the hair cells.”

The work explains side effects from aminoglycoside antibiotics, like gentamicin, notorious for ototoxicity. The drugs ramp up scramblase activity in living hair cells. That triggers membrane chaos and cell death.

Lee noted a key distinction. “Scientists initially thought these drugs caused hearing loss by blocking the channel function of TMCs in vivo,” he said. “But what we’re seeing now is that in the chaotic environment of the living hair cell, these drugs act as potent disruptors, triggering a collapse of membrane asymmetry.” Purified proteins in lab tests ignore the drugs. Factors like specific lipids or partner proteins likely amplify the effect inside cells.

Cholesterol in cell membranes tunes scramblase action, the team reported. High or low levels shift activity. That opens paths to protection via cholesterol tweaks, perhaps through diet or drugs. Such strategies might shield ears from ototoxins or genetic risks.

Yein Christina Park, a graduate student in the NIH-JHU program and co-first author, sees treatment potential. “If we understand the mechanism by which these drugs activate the scramblase, we might be able to design new drugs that lack this effect,” Park said. Antibiotics could then fight infection without silencing hearing.

The discovery spotlights membrane health in sensory cell survival. Beyond ears, scramblase roles appear in other diseases, though researchers stressed this study’s focus on hearing. Future work will probe cholesterol links and drug redesigns. Patients with TMC mutations or exposure to noisy environments stand to benefit most.