TNRC6B (trinucleotide repeat containing adaptor 6B) is a critical scaffolding protein in RNA-mediated gene silencing pathways. Its primary function involves recruiting argonaute (AGO) proteins to target mRNAs and simultaneously assembling deadenylase complexes (CCR4-NOT and PAN) to mediate both miRNA-dependent translational repression and siRNA-dependent mRNA cleavage 1234. TNRC6B accomplishes silencing through its N-terminal GW-repeat domain, which interacts with AGO1-AGO4, and its C-terminal silencing domain, which independently promotes deadenylation and mRNA degradation 5. This dual-domain architecture enables recruitment and effector function independent of AGO interaction 6. Clinically, heterozygous TNRC6B variants cause TNRC6B deficiency syndrome, characterized by global developmental delay/intellectual disability (100% of patients), speech delay (94%), fine motor delay (82%), and autism or autistic traits (76%) 7. Additional features include ADHD (65%), behavioral abnormalities, short stature, metabolic abnormalities, and dysmorphic features 8. Pathogenic variants are predominantly nonsense, frameshift, or splice-site mutations consistent with haploinsufficiency mechanisms 78. Beyond developmental disorders, TNRC6B genetic variants associate with uterine leiomyoma risk 9 and age-related hearing loss 10, while downregulation of circular TNRC6B functions as a tumor suppressor in esophageal squamous cell carcinoma 11.