Core Viewpoint - The research indicates that sleep is essential for preventing the disruption of the brain phosphoproteome, which is crucial for survival [2][3]. Group 1: Importance of Sleep - Sleep is an indispensable behavior preserved across all animal species, and long-term sleep deprivation (Pr-SD) can lead to mortality in various species [1]. - The core molecular basis linking sleep deprivation-induced lethality and sleep homeostasis in mammals remains unclear [8]. Group 2: Mechanisms and Functions of Sleep - Numerous factors affecting sleep duration or quality have been reported, including biological clock genes, neural circuits, specific kinase signaling pathways, and neurotransmitters [6]. - Research has identified several functions related to sleep, such as cognition, metabolic waste clearance, metabolism, and immune function [6]. Group 3: Research Methodology - The Disk-over-water (DOW) method is utilized to study sleep deprivation by placing animals on a disk above water, forcing them to stay awake [10]. - The study observed an "irreversible point" (PONE) state in rats during DOW experiments, characterized by irreversible mortality even after sleep deprivation is terminated [11]. Group 4: Findings on PONE State - Analysis of the PONE state revealed that the balance of the brain phosphoproteome is critical for sleep regulation and the mortality caused by Pr-SD [12]. - Mice in the PONE state were unable to enter natural sleep, and their brain phosphoproteome exhibited significant disruption, closely related to the PONE state rather than the duration of sleep deprivation [13]. Group 5: Implications for Sleep and Health - Dysfunction in brain kinases or phosphatases affects the development of the PONE state and leads to corresponding sleep abnormalities [14]. - Restorative sleep of 80 minutes daily can significantly delay cognitive decline and restore the brain phosphoproteome [14]. - The findings suggest that sleep is vital for maintaining the homeostasis of the brain phosphoproteome, and its disruption may influence lethality caused by long-term sleep deprivation [14].