NALCN (sodium leak channel, non-selective) is a voltage-sensing, pore-forming subunit of the NALCN channelosome complex that regulates neuronal excitability through constitutive sodium leak currents 1. The channelosome comprises NALCN, UNC79, UNC80, and FAM155A, with UNC79 and UNC80 forming a HEAT-repeat superhelical assembly that docks onto the NALCN-FAM155A pore complex 1. NALCN controls resting membrane potential and modulates critical physiological processes including respiratory rhythm, circadian regulation, and sensory function 2. The channel conducts monovalent cations while being blocked by physiological extracellular divalent cations and can be activated by neuropeptides like neurotensin via SRC family kinases 3. Genetic variants cause distinct neurodevelopmental syndromes: gain-of-function NALCN mutations cause congenital contractures, hypotonia, and developmental delay (CLIFAHDD), while biallelic loss-of-function variants cause infantile hypotonia with psychomotor retardation (IHPRF1) 3. Loss-of-function variants are associated with severe phenotypes including failure to thrive, central sleep apnea, and refractory epilepsy 3. UNC79 loss-of-function variants also cause neurodevelopmental disorders with intellectual disability, developmental delay, and seizures 4. Beyond neurological function, NALCN regulates epithelial cell shedding and metastatic potential in cancer, with loss-of-function mutations enriched in gastric and colorectal cancers 5.