Nucleolar protein which is involved in the integration of the 5S RNP into the ribosomal large subunit during ribosome biogenesis. In ribosome biogenesis, may also play a role in rRNA transcription (By similarity). 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. 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:21804542). 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. 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. May also inhibit cell proliferation and increase apoptosis through its interaction with NF2. May negatively regulate NPM1 by regulating its nucleoplasmic localization, oligomerization and ubiquitin-mediated proteasomal degradation. Thereby, may prevent NPM1 interaction with MYC and negatively regulate transcription mediated by the MYC-NPM1 complex. May also regulate cellular aerobic respiration. In the cellular response to viral infection, may play a role in the attenuation of interferon-beta through the inhibition of DDX58/RIG-1 (By similarity). Homooligomer. Interacts with PTEN; regulates PTEN phosphorylation and increases its stability (By similarity). Interacts with RPL11; retains RPL11 into the nucleolus (PubMed:21804542). Interacts with CDKN2A/isoform tumor suppressor ARF; the interaction is direct and promotes ARF nucleoplasmic relocalization and ubiquitin-mediated proteasomal degradation. Interacts with NPM1; the interaction is direct and competitive with MYC. Interacts with NF2 (via FERM domain); the interaction is direct. Interacts with p53/TP53 (via the oligomerization region); the interaction is direct and may prevent the MDM2-mediated proteasomal degradation of p53/TP53. Interacts with DDX58; may regulate DDX58 through USP15-mediated 'Lys-63'-linked deubiquitination. Interacts with UBTF (By similarity). In the nucleolus may be more specifically localized to the fibrillar center. Mainly nucleolar it relocalizes to the nucleoplasm under specific conditions including ribosomal stress enabling it to interact and regulate nucleoplasmic proteins like p53/TP53. Also detected in the cytosol. 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. Knockout embryos are not able to form viable blastocysts. Transgenic mice lacking the expression of Nop53 in the thymus display a dramatic reduction of the number of thymic cells and of the size of the thymus. Belongs to the NOP53 family.