Key regulator of inflammation, lipid metabolism and mitochondrion homeostasis that acts by inhibiting the activity of the ubiquitin-conjugating enzyme UBE2N/Ubc13, thereby inhibiting 'Lys-63'-linked ubiquitination (By similarity). In the nucleus, can both acts as a corepressor and coactivator of transcription, depending on the context (PubMed:24943844). Acts as a transcription coactivator in adipocytes by promoting the recruitment of PPARG to promoters: acts by inhibiting the activity of the ubiquitin-conjugating enzyme UBE2N/Ubc13, leading to stabilization of KDM4A and subsequent histone H3 'Lys-9' (H3K9) demethylation (By similarity). Promotes cholesterol efflux by acting as a transcription coactivator (PubMed:19481530). Acts as a regulator of B-cell development by inhibiting UBE2N/Ubc13, thereby restricting the activation of Toll-like receptors (TLRs) and B-cell antigen receptors (BCRs) signaling pathways (By similarity). Acts as a key mediator of mitochondrial stress response: in response to mitochondrial depolarization, relocates from the mitochondria to the nucleus following desumoylation and specifically promotes expression of nuclear-encoded mitochondrial genes (PubMed:29499132). Promotes transcription of nuclear-encoded mitochondrial genes by inhibiting UBE2N/Ubc13 (PubMed:29499132). Can also act as a corepressor as part of the N-Cor repressor complex by repressing active PPARG (PubMed:19858209, PubMed:24943844). Plays an anti-inflammatory role in macrophages and is required for insulin sensitivity by acting as a corepressor (By similarity). Plays an anti-inflammatory role during the hepatic acute phase response by interacting with sumoylated NR1H2 and NR5A2 proteins, thereby preventing N-Cor corepressor complex dissociation (PubMed:20159957). In the cytosol, also plays a non-transcriptional role by regulating insulin signaling and pro-inflammatory pathways (By similarity). In the cytoplasm, acts as a negative regulator of inflammation by inhibiting the pro-inflammatory TNF-alpha pathway; acts by repressing UBE2N/Ubc13 activity (By similarity). In the cytoplasm of adipocytes, restricts the activation of insulin signaling via inhibition of UBE2N/Ubc13-mediated ubiquitination of AKT (By similarity). Able to suppress G-protein- and mitogen-activated protein kinase-mediated signal transduction (PubMed:8943324). Acts as a tumor-suppressor in liposarcoma (PubMed:27460081). (Microbial infection) Required for efficient replication of hepatitis C virus (HCV) by promoting the interaction between VAPA and HCV virus protein NS5A. Component of the N-Cor repressor complex, at least composed of NCOR1, NCOR2, HDAC3, TBL1X, TBL1R, CORO2A and GPS2 (PubMed:11931768, PubMed:19858209, PubMed:21240272). Interacts (when sumoylated at Lys-71) with TBL1X; leading to protect GPS2 from degradation by the proteasome (PubMed:24943844, PubMed:21240272). Interacts with UBE2N; leading to inhibit UBE2N/Ubc13 activity (By similarity). Interacts with TRAF1 (By similarity). Interacts with TRAF2 (By similarity). Interacts with TRAF6 (By similarity). Interacts with PPARG (when in the liganded conformation) (By similarity). Interacts with (sumoylated) NR1H2; interaction with sumoylated NR1H2 and NR5A2 onto hepatic acute phase protein promoters prevents N-Cor corepressor complex dissociation (PubMed:20159957). Interacts with (sumoylated) NR5A2; interaction with sumoylated NR1H2 and NR5A2 onto hepatic acute phase protein promoters prevents N-Cor corepressor complex dissociation (PubMed:20159957). Interacts with NR1H3 (PubMed:19481530). Interacts with RFX4 (By similarity). Interacts with ANKRD26 (PubMed:22666460). (Microbial infection) Interacts (via coiled coil domain) with hepatitis C virus (HCV) NS5A. Sumoylation regulates the subcellular location (PubMed:24943844). Relocates from the mitochondria to the nucleus following desumoylation, leading to mediate mitochondrial stress response (By similarity). Widely expressed. Down-regulated in liposarcoma (PubMed:27460081). Down-regulated in macrophages of patients with adipose tissue inflammation and type-2 diabetes (PubMed:27270589). Sumoylation regulates its subcellular location (PubMed:24943844). Sumoylation at Lys-45 and Lys-71 regulates the shuttling between the cytoplasm and the nucleus (PubMed:24943844). Sumoylation at Lys-71 is required for interaction with TBL1X (By similarity). Sumoylated at Lys-45 and Lys-71 in mitochondrion (By similarity). Desumoylation by SENP1 leads to relocation from the mitochondria to the nucleus (By similarity). Ubiquitinated at the C-terminus by SIAH2; leading to its degradation by the proteasome. Interaction with TBL1X and methylation at Arg-323 protect GPS2 against ubiquitination and degradation. Methylated at Arg-312 and Arg-323 by PRMT6. Methylation at Arg-323 protects from degradation by the proteasome. Wrong choice of frame.