RPL5 is a structural component of the large ribosomal subunit (LSU) and functions as part of the 5S ribonucleoprotein particle (5S RNP), essential for ribosome assembly and rRNA maturation 1234. Beyond its canonical role in protein synthesis catalysis, RPL5 serves as a critical nucleolar stress sensor. When ribosome biogenesis is perturbed, RPL5 accumulates in the nucleoplasm where it inhibits MDM2, thereby stabilizing and activating the p53 tumor suppressor 4. This p53-regulatory function involves RPL5 forming a complex with RPL11 that prevents MDM2-mediated p53 ubiquitination 567. Clinically, RPL5 mutations are associated with Diamond-Blackfan anemia, a congenital bone marrow failure syndrome 89. Additionally, RPL5 deletions have been identified as genomic drivers affecting clinical outcomes in multiple myeloma 10. In ribosomopathies like Shwachman-Diamond syndrome, RPL5 mutations represent convergent somatic evolution targets that offset germline ribosomal defects through p53 pathway activation, though this increases cancer risk 11. The p53-dependent nucleolar surveillance pathway mediated by RPL5 also suppresses cancer development through ferroptosis mechanisms 6.