BRIX1 (biogenesis of ribosomes BRX1) is a nucleolar protein essential for 60S ribosomal subunit biogenesis and rRNA processing 1. Mechanistically, BRIX1 facilitates pre-rRNA processing by supporting PeBoW complex formation and promotes rDNA transcription through interactions with UBTF and POLR1A in the nucleolus 12. BRIX1 is activated by mTORC1-SP1 signaling and coordinates ribosome biogenesis with alternative splicing regulation, particularly affecting SRSF1-mediated oncogenic isoforms 2. Critically, BRIX1 suppresses p53 activation by impairing MDM2 interactions with ribosomal proteins RPL5 and RPL11, promoting chemotherapy resistance 1. In colorectal cancer, BRIX1 enhances glycolysis through selective translation of GLUT1, correlating with glucose uptake on PET-CT imaging 3. BRIX1 is significantly upregulated across multiple cancer types—hepatocellular carcinoma, colorectal cancer, and others—and associates with poor prognosis 234. Therapeutic targeting of BRIX1 via engineered exosomes induces nucleolar stress and p53-dependent tumor suppression, enhancing 5-FU chemotherapy efficacy 1. BRIX1 serves as a prognostic biomarker in HCC and appears in multi-gene prognostic signatures predicting immunotherapy response and clinical outcomes 2456.