TDRD3 is a multifunctional scaffolding protein that recognizes dimethylarginine-containing proteins through its Tudor domain 1. In the nucleus, TDRD3 acts as a transcriptional coactivator by reading asymmetric dimethylation marks (H3R17me2a and H4R3me2a) on histone tails and recruiting transcriptional machinery 2. TDRD3 forms a complex with topoisomerase 3B (TOP3B) and the helicase DHX9 to resolve R-loops at gene promoters, facilitating gene expression and preventing transcriptional blockade 3. In the cytoplasm, TDRD3 participates in stress granule assembly with G3BP1 as an antiviral factor, promoting interferon signaling and innate immune responses 4. Clinically, TDRD3 dysfunction has significant neurological implications. Tdrd3-null mice display impaired cognitive behaviors, aberrant neurogenesis, synaptic plasticity defects, hyperactivity, and anxiety changes, with defective post-transcriptional regulation of genes critical for neurodevelopment 5. Human TDRD3 variants are associated with schizophrenia, autism, cognitive disorders, and reduced educational attainment 6. Additionally, TDRD3 variants influence ovarian reserve markers in fertility contexts 7. The protein's role in cancer biology extends to hepatocellular carcinoma, where TDRD3 reads histone sulfation marks to regulate hypoxic responses 2.