RPL28 encodes a component of the large ribosomal subunit (60S) and serves as a structural constituent of the ribosome responsible for protein synthesis 123. Beyond its canonical ribosomal function, RPL28 demonstrates significant roles in disease pathogenesis and cellular regulation. In colorectal cancer, RPL28 expression is elevated in tumor tissues compared to normal tissues by up to 124%, and higher expression levels are associated with reduced survival in metastatic cases 4. Genetic variants in RPL28, particularly the rs4806668T allele, correlate with increased expression and shorter progression-free survival 4. RPL28 also modulates immune surveillance by regulating MHC class I peptide generation, with its depletion increasing both ubiquitin-dependent and -independent peptide presentation 5. Additionally, RPL28 expression is significantly decreased following exposure to environmental toxins like 4-nonylphenol, contributing to impaired spermatogenesis 6, and is upregulated in response to ammonia exposure in respiratory tissues 7. The protein has emerged as a potential biomarker for HBV-associated hepatocellular carcinoma 8, highlighting its clinical significance across multiple disease contexts beyond its fundamental ribosomal function.