DHX38 (DEAH-box helicase 38) is an ATP-dependent RNA helicase that functions as a core spliceosomal component essential for pre-mRNA splicing 1. The protein promotes splicing of both canonical and cryptic 5' splice sites and regulates alternative splicing events 1. Beyond its canonical splicing role, DHX38 maintains genome integrity by preventing R-loop accumulation and DNA damage during DNA replication stress 2. Mechanistically, DHX38 associates with key splicing factors involved in splicing steps and directly interacts with target transcripts to modulate alternative pre-mRNA splicing patterns 3. In the retina specifically, DHX38 regulates splicing of genes including FSCN2 and RHO 1, and is required for proper inner ear development through ensuring correct splicing of DNA damage repair genes 4. Clinically, DHX38 mutations cause autosomal recessive retinitis pigmentosa (RP84), a hereditary blinding disease 5. The RP-linked mutation G332D modulates DHX38 splicing activity 1. Additionally, DHX38 expression is critical for ovarian clear cell carcinoma tumorigenesis, suggesting potential therapeutic targeting in cancer 6. DHX38 is regulated post-transcriptionally by the m6A reader YTHDF1, which enhances its translation in the retina 7.