DHX30 is an ATP-dependent RNA helicase that plays critical roles in mitochondrial biogenesis and neurodevelopment 1. Its primary function involves assembly of the mitochondrial large ribosomal subunit and resolution of mitochondrial DNA G-quadruplexes, which regulate cellular glycolysis 2. DHX30 also functions as a ribosome-associated protein important for neural development 3 and is required for early embryonic development, particularly in neural cell differentiation 4. Mechanistically, DHX30 exhibits dual subcellular localization in both mitochondria and cytoplasm 2. It participates in stress granule assembly and regulates global translation through interaction with other regulatory proteins like PCBP2 5. Additionally, DHX30 interacts with pathogenic FUS protein in amyotrophic lateral sclerosis, where conformational changes impair mitochondrial translation and promote cytosolic aggregation 6. Clinically, biallelic and heterozygous DHX30 variants cause neurodevelopmental disorder with variable motor and language impairment 1. Notably, missense variants within helicase core motifs produce severe phenotypes (global developmental delay, intellectual disability, severe speech impairment, gait abnormalities) through gain-of-function mechanisms affecting stress granule formation, while loss-of-function variants cause milder presentations 1. DHX30 variants also contribute to amyotrophic lateral sclerosis pathology through mitochondrial dysfunction mechanisms.