DDX28 is a DEAD-box RNA helicase that plays an essential role in mitochondrial ribosome biogenesis, particularly in the assembly of the mitochondrial large ribosomal subunit (mt-LSU) 1. The protein resides in mitochondrial RNA granules and facilitates proper mt-LSU assembly through its RNA and Mg²⁺-dependent ATPase helicase activity, which maintains immature conformations of 16S rRNA domains during the late assembly phases 2. DDX28 directly interacts with 16S rRNA and mt-LSU components 13. Depletion of DDX28 impairs mitochondrial protein synthesis and oxidative phosphorylation complex assembly without affecting rRNA processing or mRNA stability 1. Beyond mitoribosome biogenesis, DDX28 functions as a negative regulator of hypoxia-inducible factor 2α (HIF-2α) and suppresses HIF-2α-directed eukaryotic initiation factor 4E2 (eIF4E2) translation under hypoxic conditions 4. In cancer cells with low endogenous DDX28, overexpression suppresses cell migration, spheroid growth, and invasion through alterations in cellular bioenergetics rather than HIF-2α transcriptional activity 5. Additionally, DDX28 has been identified as a hub gene and biomarker in preeclampsia risk prediction, with altered expression in placental dysfunction 6. These findings identify DDX28 as a dual-function protein linking mitochondrial metabolism to cancer biology and pregnancy pathology.