MTPAP (mitochondrial poly(A) polymerase) is a mitochondrial enzyme responsible for adding 3' poly(A) tails to mitochondrial transcripts, playing a crucial role in mitochondrial RNA processing and stability 1. The enzyme demonstrates higher activity with ATP and UTP substrates and is essential for mitochondrial mRNA polyadenylation, which differentially affects transcript stability depending on the specific mRNA species 1. Beyond polyadenylation, MTPAP participates in tRNA repair by adding the missing 3'-terminal adenosine to incomplete tRNA(Tyr) molecules that result from overlapping gene processing 2. The protein also functions as part of an autophagy receptor complex with NDP52, enhancing mitophagy - the selective removal of damaged mitochondria 3. Disease-associated mutations in MTPAP cause spastic ataxia 4 (SPAX4), characterized by the simultaneous occurrence of spastic paraplegia and cerebellar ataxia 4. Pathogenic mutations, such as p.N478D, result in severe loss of transcript polyadenylation, compromised respiratory chain complexes, and cellular radiosensitivity due to disrupted ROS homeostasis and impaired DNA repair 15. Recent studies suggest MTPAP expression may serve as a potential biomarker for major depressive disorder, showing significant upregulation in peripheral blood of patients 6.