Voltage-gated sodium (NaV) channels are critical regulators of neuronal excitability and are targeted by many toxins that directly interact with the pore-forming α subunit, typically via extracellular loops of the voltage-sensing domains, or residues forming part of the pore domain. We have recently isolated the first NaV-targeting peptide toxin, Excelsatoxin A, from the Australian stinging tree Dendrocnide excelsa. Unlike other animal venom-derived toxins, Excelsatoxin A interacts with NaV channels via TMEM233, a member of the dispanin family of transmembrane proteins expressed in sensory neurons. These findings identify TMEM233 as a previously unknown NaV-interacting protein, position TMEM233 and the dispanins as the first accessory proteins that are indispensable for toxin-mediated effects on NaV channel gating, and provide important insights into the function of NaV channels in sensory neurons.