Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. In macrophages, isoform 5 may participate in the control of podosome and invadopodia formation. The voltage-sensitive sodium channel consists of an ion conducting pore forming alpha-subunit regulated by one or more beta-1 (SCN1B), beta-2 (SCN2B), beta-3 (SCN3B) and/or beta-4 (SCN4B). Beta-1 (SCN1B) and beta-3 (SCN3B) are non-covalently associated with alpha, while beta-2 (SCN2B) and beta-4 (SCN4B) are covalently linked by disulfide bonds. Interacts with FGF13 (By similarity). Interacts with NEDD4 and NEDD4L (PubMed:15123669). Interacts with FGF14, GBG3, GBB2 and SCN1B (By similarity). Interacts with the conotoxin GVIIJ (By similarity). Interacts with the scorpion toxin BMK M1 (PubMed:20678086). Interacts with CALM1; the interaction modulates the inactivation rate of SCN8A (PubMed:23942337). Mainly localizes to the axon initial segment. Expressed in the hippocampus (at protein level) (PubMed:28842554). Expressed in brain, cerebellum and spinal cord. Isoform 5: May be expressed in non-neuronal tissues, such as peritoneal macrophages. The sequence contains 4 internal repeats, each with 5 hydrophobic segments (S1, S2, S3, S5, S6) and one positively charged segment (S4). Segments S4 are probably the voltage-sensors and are characterized by a series of positively charged amino acids at every third position. May be ubiquitinated by NEDD4L; which would promote its endocytosis. Phosphorylation at Ser-1495 by PKC in a highly conserved cytoplasmic loop slows inactivation of the sodium channel and reduces peak sodium currents. Defects in Scn8a are the cause of motor endplate disease (med). Med is a recessive neuromuscular disorder that is characterized by lack of signal transmission at the neuromuscular junction, excess preterminal arborization and degeneration of cerebellar Purkinje cells. It produces early onset progressive paralysis of hind limbs, severe muscle atrophy and juvenile lethality. Defects in Scn8a are the cause of the jolting mutant (medjo), a mild form of motor endplate disease which is characterized by the absence of spontaneous, regular, simple discharges from Purkinje cells. After 3 weeks of age, jolting mice are unsteady and have wide-based gait and a rhythmical tremor of head and neck induced by attempted movement. Defects in Scn8a are a cause of degenerating muscle (dmu). Dmu is an autosomal recessive neuromuscular disorder that is characterized by skeletal and cardiac muscle degeneration. It produces early onset progressive loss of mobility of the hind limbs and subsequent lethality in the first month of life. Due to aberrant splicing. Belongs to the sodium channel (TC 1.A.1.10) family. Nav1.6/SCN8A subfamily.