USP36 is a nucleolar deubiquitinase essential for ribosomal RNA processing and nucleolar organization 123. As a K48-linked deubiquitinase, USP36 stabilizes critical ribosome biogenesis factors including DHX33, NPM1, and FBL through deubiquitination 123. Beyond its canonical nucleolar functions, USP36 regulates transcription by deubiquitinating histone H2B at differentiation-associated gene promoters like CDKN1A 4. Notably, USP36 specifically stabilizes nucleolar MYC through interaction with FBXW7gamma, counteracting SCF(FBW7)-mediated ubiquitination 5. Additionally, USP36 functions as a SUMO ligase promoting EXOSC10 sumoylation critical for rRNA processing 6. Clinically, USP36 is significantly upregulated in multiple cancers. In breast cancer, USP36 stabilizes estrogen receptor-α, promoting tamoxifen resistance 7. In colorectal cancer, USP36 inhibits p53 signaling by stabilizing RBM28 8 and blocks apoptosis through deubiquitinating survivin and cIAP1 9. In glioblastoma, USP36 stabilizes ALKBH5, enhancing tumorigenesis and reducing temozolomide sensitivity 10. USP36 also promotes solid tumor resistance to ribosome inhibitors through JNK-dependent Snail1 stabilization 11. Elevated USP36 correlates with poor prognosis in hepatocellular carcinoma and associates with increased immune checkpoint expression 12. Outside oncology, USP36-mediated PARP1 stabilization contributes to doxorubicin-induced cardiomyopathy 13.