HSD17B7 is required for Sensory Hair Cells Function by Regulating Cholesterol Synthesis

However, the contribution of cholesterol biosynthesis to auditory physiology remains poorly understood. HSD17B7 (17β-Hydroxysteroid dehydrogenase type 7) catalyzes the conversion of zymosterone to zymosterol, a key step in the post-lanosterol cholesterol biosynthetic pathway.

Here, we found that Hsd17b7 is highly enriched in sensory hair cells of zebrafish and mice. The deficiency of Hsd17b7 led to reduced intracellular cholesterol levels in HEI-OC1 cells and zebrafish hair cells, resulting in compromised MET and acoustic startle responses. In parallel, we identified a heterozygous nonsense variant in HSD17B7 (c.544G>T; p.E182*) in an individual with bilateral profound hearing loss.