RPP21 is a core protein subunit of human ribonuclease P (RNase P), a ribonucleoprotein complex that generates mature tRNA molecules by cleaving their 5'-ends 1. The protein binds precursor tRNA and is associated with highly purified RNase P complexes 1. Mechanistically, RPP21 primarily functions as a binding element for RNase P RNA, with archaeal studies showing it binds the loop between P11 and P12 helices through positively charged surface clusters and serves as a scaffold for optimal structural conformation 2. RPP21 localizes predominantly in the nucleoplasm but can also be found in nucleoli and Cajal bodies, with its intranuclear distribution regulated by alternative splicing 1. Beyond its canonical role in tRNA processing, RPP21 has been implicated in DNA damage response, specifically in homology-directed repair of double-strand breaks, where it is recruited to DNA damage sites in a PARP1-dependent manner 3. Recent studies suggest clinical significance, as RPP21 expression is elevated in hepatocellular carcinoma tissues compared to non-tumor tissues, with high expression associated with poor overall survival 4. Additionally, RPP21 has been identified as a candidate risk gene in endometrial cancer susceptibility studies 5.