2. Academic Validation
  3. Abnormal iron homeostasis mediates cochlear hair cell impairment and hearing loss in Gprasp2-deficient mice

Abnormal iron homeostasis mediates cochlear hair cell impairment and hearing loss in Gprasp2-deficient mice

  • Commun Biol. 2026 Feb 13;9(1):425. doi: 10.1038/s42003-026-09679-8.
Yajie Lu 1,  Fanghong Sheng 2,  Jun Yao 3 2,  Qinjun Wei 3 2,  Haibing Chen 4,  Zhibin Chen 4,  Guangqian Xing 4,  Xin Cao 5 6,  Tianming Wang 7
Affiliations

Affiliations

  • 1 The Laboratory Centre for Basic Medicine Sciences, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, China. [email protected].
  • 2 Department of Medical Genetics, School of Basic Medical Science, Nanjing Medical University, Nanjing, China.
  • 3 The Laboratory Centre for Basic Medicine Sciences, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, China.
  • 4 Department of Otolaryngology, the First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
  • 5 The Laboratory Centre for Basic Medicine Sciences, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, China. [email protected].
  • 6 Department of Medical Genetics, School of Basic Medical Science, Nanjing Medical University, Nanjing, China. [email protected].
  • 7 Central Laboratory, Translational Medicine Research Center, The Affiliated Jiangning Hospital with Nanjing Medical University, Nanjing, China. [email protected].
PMID: 41688572 DOI: 10.1038/s42003-026-09679-8
Abstract

The G protein-coupled receptor associated sorting protein 2 (GPRASP2) gene mutation is one of only three deafness genes identified to be implicated in X-linked recessive syndromic hearing loss (SHL) to date. However, the function of GPRASP2 in the auditory system has not yet been fully understood. In this study, we generated Gprasp2-deficient mice and found that they exhibited a hearing loss phenotype and depression-like behaviors. In addition, we observed a disordered arrangement of cochlear hair cells in Gprasp2-deficient mice. GPRASP2 binds to NCAM1. Gprasp2 deficiency decreased NCAM1 level and further enhanced ferritinophagy in cochlear hair cells. This study could improve our understanding of the role of GPRASP2 deficiency in auditory cells, which contributes to the pathophysiology of X-linked SHL.

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