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

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.