Persistently depolarizing sodium (Na+) leak currents enhance electrical excitability,. The ion
channel responsible for the major background Na+ conductance in neurons is the Na+ leak
channel, non-selective (NALCN),. NALCN-mediated currents regulate neuronal excitability
linked to respiration, locomotion and circadian rhythm,,,,,–. NALCN activity is under tight
regulation,,–and mutations in NALCN cause severe neurological disorders and early death,.
NALCN is an orphan channel in humans, and fundamental aspects of channel assembly …

NALCN, a sodium leak channel expressed mainly in the central nervous system, is
responsible for the resting Na+ permeability that controls neuronal excitability. Dysfunctions
of the NALCN channelosome, NALCN with several auxiliary subunits, are associated with a
variety of human diseases. Here, we report the cryo-EM structure of human NALCN in
complex with FAM155A at an overall resolution of 3.1 angstroms. FAM155A forms extensive
interactions with the extracellular loops of NALCN that may help stabilize NALCN in the …