PTCD3 (pentatricopeptide repeat domain 3) is a mitochondrial RNA-binding protein that associates with the small subunit of the mitochondrial ribosome and regulates mitochondrial translation 1. Rather than affecting mRNA stability or processing, PTCD3 promotes mitochondrial protein synthesis and respiratory chain function 1. Loss of PTCD3 function impairs the activity of oxidative phosphorylation complexes I and IV, resulting in decreased mitochondrial respiration and ATP biosynthesis 2. PTCD3 deficiency causes Leigh syndrome, a severe neurological disorder presenting with psychomotor delay, respiratory insufficiency, dystonia, optic atrophy, and seizures in early infancy 32. Brain imaging shows characteristic thalamic and basal ganglia abnormalities. Pathogenic variants identified include compound heterozygous mutations affecting mRNA processing and protein truncation, with functional studies demonstrating impaired mitochondrial translation machinery function 3. Beyond inherited disease, PTCD3 has been implicated in cancer progression. PTCD3 is upregulated in colorectal and prostate cancers, where it correlates with tumor stage, metastatic potential, and poor prognosis 45. In colorectal cancer, PTCD3 promotes glutaminolysis through IGF2BP2-mediated stabilization of SLC38A2 mRNA, supporting metabolic reprogramming that facilitates cancer cell growth and metastasis 5.