Depolarizing sodium (Na⁺) leak currents carried by the NALCN channel regulate the resting membrane potential of many neurons to modulate respiration, circadian rhythm, locomotion and pain sensitivity^1–8. NALCN requires FAM155A, UNC79 and UNC80 to function, but the role of these auxiliary subunits is not understood^3,7,9–12. NALCN, UNC79 and UNC80 are essential in rodents^2,9,13, and mutations in human NALCN and UNC80 cause severe developmental and neurological disease^14,15. Since fundamental aspects about the composition, assembly, and gating of the NALCN channelosome remain obscure, we determined the structure of this ~1 megadalton complex. UNC79 and UNC80 are massive HEAT-repeat proteins that form an intertwined anti-parallel superhelical assembly which docks intracellularly onto the NALCN-FAM155A pore-forming subcomplex. Calmodulin copurifies bound to the carboxy-terminal domain of NALCN, identifying this region as a putative modulatory hub. Single channel analyses uncovered a low open probability for the wild-type complex, highlighting the tightly closed S6-gate in the structure, and providing a basis to interpret the altered gating properties of disease-causing variants. Key constraints between the UNC79-UNC80 subcomplex and the NALCN DI-DII and DII-DIII linkers are identified that lead to a model of channelosome gating. Our results provide a structural blueprint to understand NALCN channelosome physiology and a template for drug discovery to modulate the resting membrane potential.