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 (PubMed:22424771, PubMed:24953653, PubMed:28039360, PubMed:28123943, PubMed:29499132). In the nucleus, can both acts as a corepressor and coactivator of transcription, depending on the context (PubMed:18218630, PubMed:24953653, PubMed:25519902, PubMed:27270589, PubMed:28039360). 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 (PubMed:22666460, PubMed:24953653). Promotes cholesterol efflux by acting as a transcription coactivator (By similarity). 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 (PubMed:28039360). 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:25519902). Plays an anti-inflammatory role in macrophages and is required for insulin sensitivity by acting as a corepressor (PubMed:27270589). 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 (By similarity). In the cytosol, also plays a non-transcriptional role by regulating insulin signaling and pro-inflammatory pathways (PubMed:22424771, PubMed:28123943). In the cytoplasm, acts as a negative regulator of inflammation by inhibiting the pro-inflammatory TNF-alpha pathway; acts by repressing UBE2N/Ubc13 activity (PubMed:22424771). In the cytoplasm of adipocytes, restricts the activation of insulin signaling via inhibition of UBE2N/Ubc13-mediated ubiquitination of AKT (PubMed:28123943). Able to suppress G-protein- and mitogen-activated protein kinase-mediated signal transduction (By similarity). Component of the N-Cor repressor complex, at least composed of NCOR1, NCOR2, HDAC3, TBL1X, TBL1R, CORO2A and GPS2 (PubMed:25519902). Interacts (when sumoylated at Lys-71) with TBL1X; leading to protect GPS2 from degradation by the proteasome (PubMed:26070566). Interacts with UBE2N; leading to inhibit UBE2N/Ubc13 activity (PubMed:22424771). Interacts with TRAF1 (PubMed:22424771). Interacts with TRAF2 (PubMed:22424771). Interacts with TRAF6 (PubMed:22424771). Interacts with PPARG (when in the liganded conformation) (PubMed:25519902). Interacts with (sumoylated) NR1H2; interaction with sumoylated NR1H2 and NR5A2 onto hepatic acute phase protein promoters prevents N-Cor corepressor complex dissociation (By similarity). Interacts with (sumoylated) NR5A2; interaction with sumoylated NR1H2 and NR5A2 onto hepatic acute phase protein promoters prevents N-Cor corepressor complex dissociation (By similarity). Interacts with NR1H3 (By similarity). Interacts with RFX4 (PubMed:18218630). Interacts with ANKRD26 (By similarity). Sumoylation regulates the subcellular location (PubMed:29499132). Relocates from the mitochondria to the nucleus following desumoylation, leading to mediate mitochondrial stress response (PubMed:29499132). Sumoylation regulates its subcellular location (PubMed:26070566, PubMed:29499132). Sumoylation at Lys-45 and Lys-71 regulates the shuttling between the cytoplasm and the nucleus (By similarity). Sumoylation at Lys-71 is required for interaction with TBL1X (PubMed:26070566). Sumoylated at Lys-45 and Lys-71 in mitochondrion (PubMed:29499132). Desumoylation by SENP1 leads to relocation from the mitochondria to the nucleus (PubMed:29499132). 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. Embryonic lethality (PubMed:25519902). Embryonic fibroblast cells show reduced corepressor function of the N-CoR complex for PPARG, leading to constitutive activation of PPARG target genes and spontaneous adipogenesis of the cells (PubMed:25519902). Conditional knockout mice lacking Gps2 in B-cells show developmental defects at multiple stages of B-cell differentiation, caused by of aberrant activation of 'Lys-63'-linked ubiquitination events and altered gene expression programs downstream of the misregulated signaling pathways (PubMed:28039360). Conditional knockout mice lacking Gps2 in macrophages show inappropriate corepressor complex function, leading to enhancer activation, pro-inflammatory gene expression and hypersensitivity toward metabolic-stress signals (PubMed:27270589). Conditional knockout mice lacking Gps2 in adipose tissues show obesity associated with constitutive insulin signaling, increased lipid deposition in the white adipose tissue and improved systemic insulin sensitivity (PubMed:28123943). Conditional knockout mice lacking Gps2 in adipose tissues display reduced mitochondrial content in brown adipose tissue (PubMed:29499132).