DDX46 (DEAD-box helicase 46) is a RNA helicase that serves dual roles in pre-mRNA splicing and immune regulation. As a component of the 17S U2 small nuclear ribonucleoprotein (snRNP) complex, DDX46 is essential for spliceosome assembly and branch site recognition during pre-mRNA splicing 1. The protein anchors to SF3B1 within the U2 snRNP complex, where it functions mutually exclusively with DDX42 in spliceosome assembly 1. Beyond splicing, DDX46 plays a critical regulatory role in innate immunity by binding to antiviral transcripts (Mavs, Traf3, Traf6) via conserved CCGGUU elements and recruiting ALKBH5 to remove N6-methyladenosine (m6A) modifications, thereby retaining these transcripts in the nucleus and inhibiting interferon production 2. Recent studies demonstrate DDX46's involvement in B-cell receptor signaling through the ALKBH5/treRNA1/DDX46 axis, which regulates m6A demethylation and transcript processing 3. Clinically, DDX46 is overexpressed in multiple cancers including colorectal, breast, and osteosarcoma, where its knockdown inhibits proliferation, invasion, and tumor growth 456. Additionally, DDX46 contributes to temozolomide resistance in glioblastoma through CHK1-mediated phosphorylation and subsequent RNA structural remodeling 7.