In summary, thanks to the development and cost reduction of today’s genetic sequencing technology, we recommended that clinical hearing loss gene screening should include whole-gene sequencing of GJB2 and we propose that in addition to the well-established GJB2 mutations as a cause of hearing loss, it is also important to consider whether interaction of GJB2 with other genes, such as ALDH2, NQO1, TXNRD1, PRDX4 and so on, may be involved in intracellular ROS metabolism [31], resulting in more severe hearing loss or compensatory effects. Here, GJB2 is linked to hearing loss disorder.