PRORP (protein-only RNase P catalytic subunit) is the catalytic component of mitochondrial ribonuclease P, a multi-subunit protein complex essential for tRNA maturation 1. As part of the mitochondrial RNase P assembly comprising TRMT10C/MRPP1, HSD17B10/MRPP2, and PRORP/MRPP3, it catalyzes precise 5' cleavage of precursor tRNA molecules to liberate mature tRNAs 12. Unlike bacterial and nuclear RNase P enzymes that utilize catalytic RNA, PRORP achieves RNA processing through a protein-only mechanism 3. Structurally, PRORP contains PPR and nuclease domains that mediate substrate recognition and precise pre-tRNA cleavage, with the methyltransferase subcomplex positioning tRNA for processing 1. This tRNA maturation is critical for mitochondrial protein synthesis and oxidative phosphorylation, as demonstrated by evidence that impaired PRORP function prevents mitochondrial RNA processing and respiratory chain function 4. Biallelic PRORP variants cause combined oxidative phosphorylation deficiency 54 (COXPD54), an autosomal recessive disorder presenting with sensorineural hearing loss, ovarian insufficiency, and leukodystrophy 5. Missense mutations affecting the conserved metallonuclease domain reduce pre-tRNA cleavage efficiency, establishing PRORP variants as disease-causing in mitochondrial dysfunction 5.