GJB3 encodes connexin 31, a gap junction protein that forms intercellular channels enabling direct cell-to-cell communication and material transfer between adjacent cells. The protein functions primarily through gap junction formation, allowing passage of small molecules and ions between cells 1. GJB3 also interacts with cytoskeletal components α-tubulin and F-actin, playing a crucial role in maintaining genomic stability by regulating spindle orientation during cell division 2. Loss of GJB3 function leads to impaired microtubule and actin dynamics, resulting in aneuploidy and chr1 instability 2. Disease-associated mutations in GJB3 cause autosomal dominant hearing impairment, particularly high-frequency hearing loss, through disrupted gap junction communication in inner ear tissues 3. The gene is also linked to erythrokeratodermia variabilis et progressiva (EKVP), a rare skin disorder characterized by hyperkeratotic plaques and erythematous patches, where connexin variants cause multiple molecular defects including impaired gap junction formation and altered cellular turnover 14. Additionally, GJB3 downregulation in bladder cancer promotes tumor cell invasion and migration, while in breast cancer, GJB3-mediated gap junctions facilitate cAMP transfer to adipocytes, activating lipolysis and supporting tumorigenesis 25.