UBA52 encodes a fusion protein comprising ubiquitin fused to ribosomal protein L40 (rpL40), a structural component of the 60S ribosomal subunit. The gene supplies both ubiquitin and rpL40 simultaneously to the ribosome, where they form a functional complex essential for translation of specific cellular transcripts and cap-dependent translation of vesicular stomatitis virus mRNAs. UBA52 is critical for embryonic development; UBA52-deficient mice die during gestation, and cells lacking UBA52 exhibit decreased protein synthesis and cell-cycle arrest despite normal total ubiquitin levels, indicating that the fusion protein performs functions distinct from bulk ubiquitin provision. UBA52 participates in multiple disease-related pathways. In gastric adenocarcinoma, rpL40 methylation by SMYD5 at lysine 22 regulates mRNA translation to promote malignant progression 1. In Alzheimer disease, the MLKL-USP7-UBA52 axis maintains autophagy by regulating ubiquitin homeostasis; loss of this signaling disrupts neurodegenerative disease-related pathways and exacerbates cognitive impairment 2. In hepatocellular carcinoma, UBA52 knockdown induces autophagy through EMC6, suppressing tumorigenesis and migration 3. UBA52 has also emerged as a diagnostic biomarker for multiple sclerosis with high predictive accuracy 4 and correlates with survival outcomes in HCC patients 5. UBA52 additionally modulates DNA repair by antagonizing RNF168-mediated histone ubiquitination at DNA damage sites 6, and dysregulation of ubiquitination—including abnormally elevated UBA52 expression—is associated with pathological fibrosis in chr19 pulmonary diseases 7.