RRP12 (ribosomal RNA processing 12 homolog) is a nucleolar protein essential for ribosomal RNA metabolism and ribosomal subunit biogenesis. Functionally, RRP12 participates in the nucleoplasmic maturation phase of 40S pre-ribosomal subunit assembly, where it is recruited early to 90S precursors and subsequently re-positioned to facilitate head rearrangements 1. Structural studies show RRP12 localizes to late-stage human 40S assembly intermediates, contributing to distinct immature rRNA conformations during subunit head formation 2. At the molecular level, RRP12 coordinates with assembly factors TSR1, BUD23-TRMT112, and export factor SLX9 to provide export competence to pre-40S particles 1. Disease relevance has been recently established: biallelic RRP12 variants (missense mutations including p.R520C, p.E477K, p.F878L) cause autosomal recessive primary brain calcifications with infantile-onset generalized dystonia, spasticity, and widespread brain calcifications 3. Patient-derived fibroblasts show significant RRP12 protein reduction and abnormal nucleolar morphology, while zebrafish rrp12 knockdown causes severe developmental delay, crimping, and early lethality 3. Clinically, RRP12 overexpression suppresses p53 activity and promotes resistance to cytotoxic stress in cancer cells 4, suggesting RRP12 targeting may enhance chemotherapy efficacy. Additionally, RRP12 appears dysregulated in hepatocellular carcinoma and colorectal cancer, identifying it as a potential biomarker and therapeutic target 56.