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Hair cell development and function are tightly regulated, and hair cell deficits are the main reasons for hearing loss and balance disorders. TMCC2 is an endoplasmic reticulum (ER)-residing transmembrane protein whose physiological function largely remains unknown. In the present work, we show that Tmcc2 is specifically expressed in the auditory hair cells of mouse inner ear. Tmcc2 knockout mice were then established to investigate its physiological role in hearing. Auditory brainstem responses measurements show that Tmcc2 knockout mice suffer from congenital hearing loss. Further investigations reveal progressive auditory hair cell loss in the Tmcc2 knockout mice. The general morphology and function of ER are unaffected in Tmcc2 knockout hair cells. However, increased ER stress was observed in Tmcc2 knockout mice and knockdown cells, suggesting that loss of TMCC2 leads to auditory hair cell death through elevated ER stress.<\/jats:p>","DOI":"10.1093\/hmg\/ddad003","type":"journal-article","created":{"date-parts":[[2023,1,8]],"date-time":"2023-01-08T05:53:00Z","timestamp":1673157180000},"page":"1622-1633","source":"Crossref","is-referenced-by-count":7,"title":["Loss of TMCC2 activates endoplasm reticulum stress and causes auditory hair cell death"],"prefix":"10.1093","volume":"32","author":[{"given":"Rui","family":"Ren","sequence":"first","affiliation":[{"name":"Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology and Key Laboratory for Experimental Teratology of the Ministry of Education , School of Life Sciences, , Qingdao, Shandong 266237 , P. R. China"},{"name":"Shandong University , School of Life Sciences, , Qingdao, Shandong 266237 , P. R. 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