Scn4b, encoding voltage-gated sodium channel β subunit, is involved in regulating neuronal activity by modulating channel gating [1]. It may also play a role in the voltage-gated cardiac sodium channel complex, which is responsible for the generation and conduction of the cardiac action potential [6].

Genetic global knockout (KO) of Scn4b in mice showed no difference in ethanol consumption but an extended duration of the loss of righting reflex induced by ethanol, gaboxadol, pentobarbital, and ketamine, suggesting its involvement in the acute hypnotic effects of these sedatives [1].

In cancer research, in breast cancer, reducing β4 (encoded by Scn4b) expression increased RhoA activity, potentiated cell migration, invasiveness, primary tumour growth, and metastatic spreading, indicating Scn4b/β4 as a metastasis-suppressor gene [5]. In non-small cell lung cancer (NSCLC), SCN4B is downregulated in tumour tissues and is associated with poor prognosis. Overexpression of SCN4B in NSCLC cells inhibited cell viability and induced apoptosis, and it may act via inhibiting the cGMP-PKG signaling pathway [2,4]. In classical papillary thyroid cancer, preserved SCN4B expression was an independent indicator of favorable recurrence-free survival, and its expression might be suppressed by DNA hypermethylation [3].

In conclusion, Scn4b is crucial in regulating neuronal and cardiac functions. Its role in diseases, especially in cancer metastasis and prognosis, has been revealed through gene knockout mouse models. These findings provide important insights into the biological functions of Scn4b and potential therapeutic targets for related diseases.