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However, the contribution of cholesterol biosynthesis to auditory physiology remains poorly understood. HSD17B7 (17\u03b2-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 reduced intracellular cholesterol levels in HEI-OC1 cells and zebrafish hair cells, thereby compromising MET and acoustic startle responses. A heterozygous nonsense variant (c.544G&gt;T; p.E182*) in\n                    <jats:italic>HSD17B7<\/jats:italic>\n                    was identified in an individual with bilateral profound hearing loss. mRNA of c.544G&gt;T HSD17B7 failed to rescue the impaired MET and acoustic startle response of hsd17b7 mutants. Mechanistically, the mutation decreases mRNA abundance and significantly reduces protein. Moreover, expression of the p.E182* mutation disrupted the interaction between HSD17B7 and the ER retention receptor RER1, leading to aberrant subcellular localization and altered cholesterol distribution, thereby exacerbating HC dysfunction. Together, our findings suggest a conserved and essential role for HSD17B7-mediated cholesterol biosynthesis in sensory hair cell function and identify HSD17B7 as a candidate gene for sensorineural hearing loss.\n                  <\/jats:p>","DOI":"10.7554\/elife.108108","type":"journal-article","created":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T14:30:28Z","timestamp":1763476228000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.108108","source":"Crossref","is-referenced-by-count":0,"title":["HSD17B7 is required for the function of sensory hair cells by regulating cholesterol synthesis"],"prefix":"10.7554","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8296-525X","authenticated-orcid":true,"given":"Yuqian","family":"Shen","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02afcvw97","id-type":"ROR","asserted-by":"publisher"}],"name":"Co-innovation Center of Neuroregeneration, School of Life Sciences, Nantong Laboratory of Development 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