PTCD2 (pentatricopeptide repeat domain 2) is a mitochondrial RNA-binding protein essential for post-transcriptional regulation of mitochondrial gene expression. PTCD2 functions as a translational regulator that facilitates the recruitment of specific mitochondrial mRNAs to the mitochondrial ribosome, with demonstrated roles in regulating translation of cytochrome b and COIII mRNAs 1. The protein also participates in RNA transcript processing, as evidenced by its involvement in proper maturation of mitochondrial DNA-encoded transcripts; PTCD2 depletion leads to accumulation of unprocessed ND5-CYTB pre-transcripts and reduced cytochrome b expression 2. Loss of PTCD2 function specifically impairs respiratory chain complex III and IV activity by reducing expression of critical subunits, resulting in profound cardiac pathology with replacement of ventricular cardiomyocytes by fibro-fatty tissue 2. Clinically, PTCD2 dysfunction may contribute to heart failure etiology 2. A CpG site mapping to PTCD2 (cg25769469) was associated with incident coronary heart disease and myocardial infarction in epigenome-wide studies, though methylation risk scores did not improve disease prediction 3. Additionally, PTCD2 has been identified as an autoantigen in Alzheimer's disease, where citrullinated PTCD2 accumulates in affected brain regions 4.