FASTKD3 is a mitochondrial RNA-binding protein essential for regulating mitochondrial gene expression and respiration. Functionally, FASTKD3 stabilizes specific mature mitochondrial mRNAs (MT-ND2, MT-ND3, MT-CYTB, MT-CO2, and MT-ATP8/6) by increasing their steady-state levels and half-lives 1. Additionally, FASTKD3 promotes MT-CO1 mRNA translation and facilitates mitochondrial complex IV assembly and activity 1. The protein contains a conserved RNA-binding domain (RAP domain) required for its mRNA stability function 1. Mechanistically, FASTKD3 knockdown severely impairs basal and stress-induced mitochondrial oxygen consumption without disrupting respiratory chain complex assembly, suggesting it functionally couples mitochondrial protein synthesis to respiration 2. Unlike other FASTK family members, FASTKD3 does not localize to mitochondrial RNA granules, indicating a distinct subcellular function 1. Disease relevance includes potential involvement in cancer pathology, with FASTKD3 amplifications identified in over 8% of lung cancers 3. Additionally, FASTKD3 transcriptomic disruption correlates with microbial dysbiosis and epigenetic alterations in HIV-associated COPD pathogenesis 4. These findings position FASTKD3 as a critical regulator of mitochondrial bioenergetics with implications for metabolic diseases and malignancy.