The molecular basis of mammalian sleep-wake regulation remains largely unexplored. Several studies have identified sleep-promoting kinases, strongly suggesting that protein phosphorylations play a critical role in driving sleep-wake cycle(Diering, 2017; Wang, 2018; BrĂ¼ning, 2019). It has been suggested that kinases such as CaMKII are activated during wakefulness and induce sleep (Tone, Ode, Zhang, 2021), but the regulation of phosphorylations involved in the induction and/or maintenance of wakefulness remains unknown. Here, we identified a novel gene involved in the maintenance of wake. This geneX is known to control protein phosphorylation in various cellular signaling pathway. AAV-mediated exogenous expression of geneX in neurons of the whole mouse brain inhibited the transition from wakefulness to sleep, resulting in a significant increase in wake duration. Conversely, inhibition of ProteinX (encoded by geneX) function in neurons increased the transition from wakefulness to sleep and decreased wake duration. Furthermore, the ProteinX-inhibited mice also showed reduced wake response to the external stimuli during sleep. These results imply that the geneX is a key regulator of signaling involved in the wake maintenance and also in the induction of acute arousal during sleep.