CLRN2 encodes a tetraspan protein essential for mammalian hearing function. Mechanistically, clarin-2 maintains stereocilia bundle integrity and mechano-electrical transduction in cochlear hair cells 1. While not required for initial stereocilia formation, clarin-2 is critical for preserving bundle structure and function during differentiation; its absence leads to progressive loss of transducing stereocilia and mechano-electrical transduction deficits 1. Additionally, clarin-2 regulates synaptic organization and ionic homeostasis 2, with synaptic auditory abnormalities observed in clarin-2-deficient mice 3. Clinically, biallelic CLRN2 variants cause autosomal recessive non-syndromic progressive hearing loss ranging from moderate to profound 45. CLRN2 is associated with age-related hearing impairment, identified as a genome-wide significant locus in UK Biobank analysis of over 250,000 individuals 6. Notably, clarin-1 and clarin-2 exhibit functional compensation; CLRN2 variants may exacerbate hearing loss in Usher syndrome type III (USH3) patients carrying CLRN1 mutations 2. Gene therapy using viral-mediated CLRN2 delivery effectively preserved hearing in deficient mice, with optimal outcomes when administered before stereocilia loss 3, suggesting therapeutic potential for CLRN2-associated post-lingual hearing impairment.