DHX36 (DEAH-box helicase 36) is a multifunctional ATP-dependent helicase that primarily functions to resolve G-quadruplex (G4) structures in both DNA and RNA 1. The enzyme binds with high affinity to G4 structures formed by guanine-rich sequences and catalyzes their unwinding, which is essential for maintaining genomic stability 2. Mechanistically, DHX36 plays a critical role during DNA replication by mediating bypass of the replicative helicase CMG past G4 structures, working in conjunction with FANCJ helicase to ensure faithful G4 replication 3. The protein also participates in G-loop disassembly mechanisms that control G4 landscapes through coordinated assembly and unwinding processes 4. Beyond its structural role, DHX36 regulates gene expression through multiple pathways. It induces transcriptome-wide RNA structural remodeling, particularly in 3'UTR regions, affecting mRNA stability through interactions with m6A modifications and YTHDF1 binding 5. Loss of DHX36 results in widespread changes in gene expression, particularly affecting transcription factors and oncogenes 6. Clinically, DHX36 deficiency leads to genome instability, accumulation of DNA double-strand breaks at G4 sites, and activation of innate immune signaling pathways including NF-κB and STING1 7. Higher DHX36 expression correlates with improved survival in B-cell acute lymphoblastic leukemia, highlighting its tumor suppressive role 7.