Protein phosphatase 1 regulatory subunit 3F (PPP1R3F)

Protein phosphatase 1 regulatory subunit 3F (PPP1R3F) is a glycogen-targeting regulatory subunit for protein phosphatase 1 (PP1), a major serine/threonine phosphatase that regulates numerous cellular processes[2][3][5]. PPP1R3F is primarily expressed in brain astrocytes and localizes to the endoplasmic reticulum, where it anchors the PP1 catalytic subunit for precise control of glycogen metabolism in neural cells[3][4]. The subunit directs PP1 to dephosphorylate enzymes such as glycogen synthase and glycogen phosphorylase, thus playing an essential role in maintaining brain glycogen levels, especially under fluctuating glucose conditions[3][4]. Genetic variants in PPP1R3F are associated with a novel X-linked neurodevelopmental disorder characterized by developmental delay, intellectual disability, autism spectrum features, and seizures[3][4][5]. Additionally, PPP1R3F gene methylation is associated with increased colorectal cancer risk, highlighting its relevance as a potential epigenetic biomarker[2]. As a regulatory (non-catalytic) protein, PPP1R3F modulates the localization and substrate specificity of PP1 but is not itself a receptor, enzyme, or transporter in the classical sense[2][3][5]. No approved drugs target PPP1R3F directly; however, its role in central nervous system metabolism and disease biology continues to be elucidated.

Other names

R3FHb2EHB2ELL0XNC01-7P3.1protein phosphatase 1, regulatory (inhibitor) subunit 3Fprotein phosphatase 1 regulatory subunit 3F

Regulation of PP1 catalytic subunit localization and activity; modulating dephosphorylation of glycogen-metabolism enzymes (e.g., glycogen synthase and glycogen phosphorylase) via scaffolding/targeting; indirectly modifiable by protein kinase A (PKA)–mediated phosphorylation of the subunit, disrupting its interaction with PP1