PPP1R3G is a regulatory subunit of protein phosphatase 1 (PP1) with dual roles in metabolic and cell death signaling. Primarily, PPP1R3G functions as a glycogen-targeting subunit that couples hepatic glycogenesis to the fasting-feeding cycle 1. Upon insulin stimulation, AKT phosphorylates PPP1R3G, enhancing its binding to and dephosphorylation of glycogen synthase, thereby promoting hepatic glycogen deposition and glucose clearance 1. This insulin-signaling cascade operates independently of GSK3-mediated pathways. Beyond metabolism, PPP1R3G recruits PP1γ to RIPK1 complex I, removing inhibitory phosphorylations that suppress RIPK1 kinase activity 2. This mechanism is essential for TNF-induced apoptosis and necroptosis, as Ppp1r3g-knockout mice show protection from inflammatory shock 2. Clinically, PPP1R3G downregulation contributes to pre-eclampsia pathogenesis by suppressing trophoblast invasion and migration via the Akt/MMP-9 signaling axis 3. Conversely, elevated PPP1R3G expression in lung adenocarcinoma correlates with poor prognosis and enhanced immune infiltration 4. PPP1R3G is also regulated by locus coeruleus-noradrenaline signaling in astrocytes during stress responses 5, suggesting broader roles in neurometabolic stress adaptation.