SCN3B encodes the β3 auxiliary subunit of voltage-gated sodium (Nav) channels, serving as a crucial regulatory component that modulates channel trafficking, localization, and functional properties in excitable tissues 1. The protein primarily functions to modulate cardiac sodium channel activity, particularly affecting SCN5A/Nav1.5 channels by causing loss-of-function effects that reduce sodium current density 1. Mechanistically, SCN3B can be regulated by inflammatory mediators like IL-2, which upregulates its transcription through p53-dependent pathways and increases sodium current density in cardiac cells 2. The gene shows tissue-specific regulation, with GATA4 serving as a transcriptional regulator in cardiac tissue 3. Disease associations include cardiac arrhythmias, where loss-of-function mutations in SCN3B contribute to early-onset lone atrial fibrillation by reducing sodium current 1, and gain-of-function promoter variants can also cause atrial fibrillation 3. Recently, biallelic truncating variants have been linked to neurodevelopmental disorders with intellectual disability, autism, and seizures 4. Interestingly, SCN3B also functions independently of ion channel activity in cancer contexts, where it acts as a tumor suppressor by inhibiting cell migration through modulation of actin cytoskeleton organization 56. Clinical significance extends beyond cardiac disorders to potential therapeutic targets in colorectal cancer 7 and epilepsy 8.