PPP1R3F encodes a glycogen-targeting subunit of protein phosphatase 1 (PP1) that regulates brain glucose homeostasis and neurological function 1. As a member of the glycogen targeting subunits (GTSs), PPP1R3F binds PP1 through a classical RVxF motif and localizes to the endoplasmic reticulum and membranes in brain astrocytes 2. The protein regulates glycogen synthase activity in response to glucose fluctuations and extracellular signals (adenosine, noradrenaline), maintaining steady brain glycogen levels under changing metabolic conditions 2. Hemizygous PPP1R3F variants cause X-linked neurodevelopmental disorder characterized by developmental delay, intellectual disability, autism spectrum disorder features, and seizures, with functional defects including impaired PP1 binding, protein instability, and abnormal glycogen metabolism regulation 1. Network analysis identifies PPP1R3F as a master transcriptional regulator in autism, affecting endocytosis pathways 3. Rare variants in PPP1R3F have been identified in autism spectrum disorder and schizophrenia cohorts, suggesting disease involvement in these neurodevelopmental conditions 4. Beyond neurology, PPP1R3F hypermethylation associates with increased colorectal cancer risk, particularly with dietary interactions 5.