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In the past two decades, transmembrane inner ear (TMIE) protein has received a great deal of research interest because its impairments cause hereditary deafness in humans. This evolutionarily conserved membrane protein contributes to a fundamental complex that plays role in the maintenance and function of the sensory hair cells. Although the critical roles of the TMIE in mechanoelectrical transduction or hearing procedures have been discussed, there are little to no review papers summarizing the roles of the TMIE in the auditory system. In order to fill this gap, herein, we discuss the important roles of this protein in the auditory system including its role in mechanotransduction, olivocochlear synapse, morphology and different signalling pathways; we also review the genotype\u2010phenotype correlation that can per se show the possible roles of this protein in the auditory system.<\/jats:p>","DOI":"10.1111\/jcmm.16610","type":"journal-article","created":{"date-parts":[[2021,5,14]],"date-time":"2021-05-14T05:44:21Z","timestamp":1620971061000},"page":"5869-5883","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["How Transmembrane Inner Ear (TMIE) plays role in the auditory system: A mystery to us"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6303-1750","authenticated-orcid":false,"given":"Mohammad","family":"Farhadi","sequence":"first","affiliation":[{"name":"ENT and Head and Neck Research Center and Department The Five Senses Health Institute Hazrat Rasoul Akram Hospital Iran University of Medical Sciences Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9926-3975","authenticated-orcid":false,"given":"Ehsan","family":"Razmara","sequence":"additional","affiliation":[{"name":"Australian Regenerative Medicine Institute Monash University Clayton VIC Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maryam","family":"Balali","sequence":"additional","affiliation":[{"name":"ENT and Head and Neck Research Center and Department The Five Senses Health Institute Hazrat Rasoul Akram Hospital Iran University of Medical Sciences Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yeganeh","family":"Hajabbas Farshchi","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Biology Tehran Medical Sciences Islamic Azad University Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2800-4199","authenticated-orcid":false,"given":"Masoumeh","family":"Falah","sequence":"additional","affiliation":[{"name":"ENT and Head and Neck Research Center and Department The Five Senses Health Institute Hazrat Rasoul Akram Hospital Iran University of Medical Sciences Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,5,13]]},"reference":[{"key":"e_1_2_15_2_1","doi-asserted-by":"publisher","DOI":"10.1080\/15513815.2019.1627625"},{"issue":"9","key":"e_1_2_15_3_1","first-page":"1237","article-title":"The prevalence of hearing impairment by age and gender in a population\u2010based study","volume":"46","author":"Asghari A","year":"2017","journal-title":"Iran J Public Health"},{"key":"e_1_2_15_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-016-1648-8"},{"key":"e_1_2_15_5_1","doi-asserted-by":"publisher","DOI":"10.2471\/BLT.19.224683"},{"key":"e_1_2_15_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijporl.2015.05.035"},{"key":"e_1_2_15_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijporl.2020.109901"},{"key":"e_1_2_15_8_1","doi-asserted-by":"publisher","DOI":"10.2147\/CIA.S109110"},{"issue":"1","key":"e_1_2_15_9_1","first-page":"49","article-title":"The anticipation and inheritance pattern of c.487A>G mutation in the GJB2 gene","volume":"15","author":"Falah M","year":"2012","journal-title":"Arch Iran Med"},{"issue":"3","key":"e_1_2_15_10_1","first-page":"213","article-title":"Profile of Iranian GJB2 mutations in young population with novel mutation","volume":"14","author":"Falah M","year":"2011","journal-title":"Iran J Basic Med Sci"},{"key":"e_1_2_15_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2018.08.006"},{"key":"e_1_2_15_12_1","unstructured":"ShearerAE HildebrandMS SmithRJ.Hereditary hearing loss and deafness overview. 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