SCN9A encodes Nav1.7, the pore-forming alpha subunit of a voltage-gated sodium channel essential for action potential generation in excitable cells 1. The channel mediates sodium ion influx along the electrochemical gradient, enabling membrane depolarization and electrical signal propagation 2. Nav1.7 is strongly expressed in nociceptive neurons, where it plays a critical and non-redundant role in pain signal transmission 3. Loss-of-function SCN9A mutations cause congenital inability to experience pain, a rare condition where affected individuals completely lack nociception despite normal overall health 3. In contrast, gain-of-function mutations produce excessive nociceptor excitability, resulting in primary erythermalgia and paroxysmal extreme pain disorder (PEPD), characterized by severe, treatment-refractory burning pain in specific anatomical regions 4. Gain-of-function mutations correlating with greater hyperpolarizing shifts in Nav1.7 correlate with earlier symptom onset 5. SCN9A variants also contribute to small fiber neuropathy, affecting thinly myelinated and unmyelinated pain-sensing fibers 6. Despite historical inclusion in epilepsy gene panels, SCN9A is not associated with monogenic epilepsy—high-frequency variants exist in asymptomatic populations, and pathogenic classifications lack supporting clinical evidence 7. These findings position Nav1.7 as a promising selective target for novel analgesic development.