PPP1R3D (protein phosphatase 1 regulatory subunit 3D) functions as a glycogen-targeting subunit that recruits protein phosphatase 1 (PP1) to glycogen particles, thereby regulating glycogen metabolism 1. The protein contains conserved functional domains: an N-terminal RVXF motif for PP1 binding, a C-terminal region (W267DNND) for substrate recognition, and a 14-3-3 binding site (RARS74LP) that negatively regulates its glycogenic activity 1. PPP1R3D promotes glycogen synthesis by dephosphorylating glycogen synthase and inhibiting glycogen phosphorylase 2. Its interaction with AMPK-β2 is dynamically regulated by intracellular glycogen content, linking energy metabolism sensing to glycogen homeostasis 3. Clinically, PPP1R3D relevance spans multiple pathologies. In Lafora disease, a fatal epilepsy characterized by pathological glycogen accumulation, PPP1R3D deficiency eliminates approximately 50% of neuronal Lafora bodies and 90% of cardiac Lafora bodies, suggesting therapeutic potential 2. During acute peanut allergic reactions, PPP1R3D is identified as a key driver gene modulating pro-inflammatory coexpression networks 4. PPP1R3D is also involved in metabolic responses to environmental toxins and stress: it is upregulated during noradrenaline-mediated stress responses in hippocampal astrocytes 5, differentially expressed in gestational PFBS exposure affecting glucose homeostasis 6, and associated with osteoarthritis pathogenesis 7. Additionally, PPP1R3D suppression by miR-4301 enhances rotavirus replication by reducing glycogen synthesis 8.