PDZD7 is a PDZ domain-containing scaffold protein essential for inner ear hair cell development and function through its role in organizing the ankle-link complex (ALC) at stereocilia 1. The protein contains three PDZ domains and a harmonin homology domain (HHD) that mediates membrane targeting 2. PDZD7 specifically localizes to the ankle region of developing stereocilia, where it forms the ALC together with USH2A, WHRN, and ADGRV1 through liquid-liquid phase separation 3. The long isoform of PDZD7 is specifically required for proper ankle-link formation and stereocilia development, as deletion of this isoform in mice causes stereocilia disorganization, reduced mechanotransduction currents, and hearing loss 1. PDZD7 also regulates USH2A protein stability by blocking adenylate cyclase inhibition mediated by ADGRV1, which affects cAMP-PKA signaling and subsequent WHRN phosphorylation 4. Mutations in PDZD7 contribute to Usher syndrome through digenic inheritance, acting as a modifier of retinal disease severity when combined with mutations in other Usher syndrome genes like USH2A and GPR98 5. The protein is associated with autosomal recessive deafness (DFNB57) and Usher syndrome types 2A and 2C, highlighting its clinical significance in hereditary hearing and vision disorders.