SYNE4 encodes nesprin-4, a nuclear envelope protein that functions as a component of the LINC (Linker of Nucleoskeleton and Cytoskeleton) complex, connecting the nuclear lamina to the cytoskeleton 1. The protein localizes to the outer nuclear membrane and is essential for proper nuclear positioning in cells 1. Mechanistically, nesprin-4 acts as a kinesin-1 cargo through a conserved 4-amino acid motif, enabling microtubule-dependent nuclear positioning 2. This interaction is particularly critical in cochlear outer hair cells (OHCs), where nesprin-4 mediates basal nuclear localization necessary for cell viability and function 2. SYNE4 mutations cause autosomal recessive deafness (DFNB76), characterized by progressive high-frequency sensorineural hearing loss 13. In affected individuals and mouse models, SYNE4 deficiency leads to nuclear mislocalization in OHCs, followed by cell degeneration and hearing loss that coincides with the onset of electromotility 12. The therapeutic potential has been demonstrated through successful AAV gene therapy in neonatal Syne4-/- mice, which restored auditory function and hair cell morphology 4. Additionally, SYNE4 expression is regulated by transcriptional machinery involving GAS41, BRD2, and the Mediator complex, highlighting its role in nuclear shape maintenance 5.