METAP1D encodes a mitochondrial methionyl aminopeptidase that removes N-terminal methionine from nascent proteins, particularly when the second residue is small and uncharged 1. Structural studies reveal that while METAP1D shares active site features with cytosolic MetAP1, it contains distinct structural differences in active-site pocket loops that may accommodate mitochondria-specific substrates 1. The enzyme requires cobalt as the optimal metal activator and exhibits lower catalytic efficiency compared to cytosolic methionine aminopeptidases 2. METAP1D demonstrates significant disease relevance across multiple conditions. Its DNA methylation serves as a promising liquid biopsy biomarker for colorectal cancer screening with 100% specificity when combined with COL25A1 3. Multi-omics Mendelian randomization studies implicate METAP1D in cerebral small vessel disease pathogenesis, showing associations with cognitive performance and dementia risk 4. The gene also contributes to idiopathic pulmonary fibrosis susceptibility 5 and major depressive disorder through protective effects at transcript and protein levels 6. Additionally, METAP1D variants may influence penetrance of Leber's hereditary optic neuropathy 7 and carotid plaque development 8. These findings highlight METAP1D's critical role in mitochondrial protein processing and its involvement in diverse pathological processes.