Nucleolar protein which is involved in the integration of the 5S RNP into the ribosomal large subunit during ribosome biogenesis (PubMed:24120868). In ribosome biogenesis, may also play a role in rRNA transcription (PubMed:27729611). Also functions as a nucleolar sensor that regulates the activation of p53/TP53 in response to ribosome biogenesis perturbation, DNA damage and other stress conditions (PubMed:21741933, PubMed:24120868, PubMed:27829214). DNA damage or perturbation of ribosome biogenesis disrupt the interaction between NOP53 and RPL11 allowing RPL11 transport to the nucleoplasm where it can inhibit MDM2 and allow p53/TP53 activation (PubMed:24120868, PubMed:27829214). It may also positively regulate the function of p53/TP53 in cell cycle arrest and apoptosis through direct interaction, preventing its MDM2-dependent ubiquitin-mediated proteasomal degradation (PubMed:22522597). Originally identified as a tumor suppressor, it may also play a role in cell proliferation and apoptosis by positively regulating the stability of PTEN, thereby antagonizing the PI3K-AKT/PKB signaling pathway (PubMed:15355975, PubMed:16971513, PubMed:27729611). May also inhibit cell proliferation and increase apoptosis through its interaction with NF2 (PubMed:21167305). May negatively regulate NPM1 by regulating its nucleoplasmic localization, oligomerization and ubiquitin-mediated proteasomal degradation (PubMed:25818168). Thereby, may prevent NPM1 interaction with MYC and negatively regulate transcription mediated by the MYC-NPM1 complex (PubMed:25956029). May also regulate cellular aerobic respiration (PubMed:24556985). In the cellular response to viral infection, may play a role in the attenuation of interferon-beta through the inhibition of DDX58/RIG-1 (PubMed:27824081). Homooligomer (PubMed:24735870, PubMed:26903295). Interacts with PTEN; regulates PTEN phosphorylation and increases its stability (PubMed:15355975). Interacts with RPL11; retains RPL11 into the nucleolus (PubMed:24556985, PubMed:27829214). Interacts with CDKN2A/isoform tumor suppressor ARF; the interaction is direct and promotes ARF nucleoplasmic relocalization and ubiquitin-mediated proteasomal degradation (PubMed:27323397). Interacts with NPM1; the interaction is direct and competitive with MYC (PubMed:25956029). Interacts with NF2 (via FERM domain); the interaction is direct (PubMed:21167305). Interacts with p53/TP53 (via the oligomerization region); the interaction is direct and may prevent the MDM2-mediated proteasomal degradation of p53/TP53 (PubMed:22522597). Interacts with DDX58; may regulate DDX58 through USP15-mediated 'Lys-63'-linked deubiquitination (PubMed:27824081). Interacts with UBTF (PubMed:27729611). (Microbial infection) Interacts with herpes simplex virus 1 early proteins ICP22 and ICP0. (Microbial infection) Interacts with Human herpesvirus 8 protein ORF16; may sequester ORF16 in host nucleolus and reduce its antiapoptotic activity. In the nucleolus may be more specifically localized to the fibrillar center (PubMed:27729611). Mainly nucleolar it relocalizes to the nucleoplasm under specific conditions including ribosomal stress enabling it to interact and regulate nucleoplasmic proteins like p53/TP53 (PubMed:22522597, PubMed:24923447, PubMed:27323397, PubMed:26903295). Also detected in the cytosol (PubMed:24923447, PubMed:27824081). Expressed at high levels in heart and pancreas, moderate levels in placenta, liver, skeletal muscle, and kidney, and low levels in brain and lung. Down-regulated by nucleolar stress through ubiquitin-independent proteasomal degradation (at protein level) (PubMed:24923447). Up-regulated upon mitochondrial stress (at protein level) (PubMed:24556985). Expression of the protein might be regulated by DNA damage but results are not consistent (PubMed:21741933, PubMed:27829214). Ubiquitin-mediated proteasomal degradation is regulated by c-JUN. It is associated with relocalization to the nucleoplasm and decreased homooligomerization. Phosphorylated upon DNA damage probably by ATM and DNA-PK; may regulate NOP53 degradation. Belongs to the NOP53 family.