FASTKD1 is a mitochondrial RNA-binding protein that primarily functions as a negative regulator of mitochondrial MT-ND3 mRNA levels, thereby modulating respiratory complex I abundance and activity 1. As a member of the FASTK protein family, FASTKD1 participates in post-transcriptional regulation of mitochondrial gene expression through its conserved RAP domain, which contains nuclease-fold activity essential for RNA targeting and processing 12. Mechanistically, FASTKD1 protects cells against oxidative stress-induced death by promoting mitochondrial homeostasis 3. FASTKD1 overexpression decreases Complex-I-dependent respiration and induces mitochondrial fragmentation independent of the mitochondrial permeability transition pore, while also inhibiting autophagy/mitophagy 3. These protective effects occur through CypD-independent pathways and have been demonstrated in both fibroblasts and cardiac myocytes 3. Clinically, FASTKD1 variants are associated with neurodegenerative disease susceptibility. Mendelian randomization analysis identified FASTKD1 as a causal gene specifically linked to frontotemporal dementia with motor neuron disease (FTD_MND) 4. Additionally, a protective FASTKD1 variant (rs12618227) showed reduced frequency in patients with immediate hypersensitivity reactions to iodinated contrast media, suggesting a role in immune-metabolic regulation 5.