Gjb3, also known as Gap Junction Protein Beta 3, encodes Connexin31 protein (Cx31). Connexins are membrane-expressed proteins that assemble into hexamers to transfer metabolites and secondary messengers. Gap junctions formed by connexins are channels for ion recycling and homeostasis, playing significant roles in human skin and cochlea [4,5,6].

Gjb3 has been implicated in multiple diseases. In cancer, it is widely expressed in various cancers and correlates with disease stages, patient survival, immunotherapy response, and pharmaceutical guidance. Knockdown of Gjb3 inhibits the PI3K/AKT pathway, reducing cancer cell proliferation, migration, and viability, suggesting it as a potential biomarker and therapeutic target, especially in lung adenocarcinomas, mesothelioma, and pancreatic adenocarcinoma [1]. In pancreatic cancer, Gjb3 promotes liver metastasis by enhancing neutrophil polarization and survival [2]. In lung adenocarcinoma, high Gjb3 expression is associated with worse prognosis, and it correlates with immune cell infiltration and immune checkpoint expression [3]. Additionally, Gjb3 mutations are involved in non-syndromic hearing loss, erythrokeratodermia variabilis (EKV), and neuropathy diseases [4,5,6].

In conclusion, Gjb3 is crucial for normal cellular communication through its role in forming gap junctions. Its dysregulation is associated with multiple diseases, especially cancer and genetic disorders like hearing loss and EKV. Studies on Gjb3, including those using loss-of-function models, contribute to understanding disease mechanisms and identifying potential therapeutic targets.