The zebrafish mutant implicates sodium homeostasis in sleep regulation.

Sleep is a nearly universal feature of animal behaviour, yet many of the molecular, genetic, and neuronal substrates that orchestrate sleep/wake transitions lie undiscovered. Employing a viral insertion sleep screen in larval zebrafish, we identified a novel gene, (), whose loss results in behavioural hyperactivity and reduced sleep at night. The neuronally expressed gene is conserved across vertebrates and encodes a small single-pass transmembrane protein that is structurally similar to the Na,K-ATPase regulator, FXYD1/Phospholemman. Disruption of either or , a Na,K-ATPase alpha-3 subunit associated with several heritable movement disorders in humans, led to decreased night-time sleep. Since and mutants have elevated intracellular Na levels and non-additive effects on sleep amount at night, we propose that Dmist-dependent enhancement of Na pump function modulates neuronal excitability to maintain normal sleep behaviour.