TRIM71 is an E3 ubiquitin-protein ligase and RNA-binding protein essential for developmental processes. It cooperates with the miRNA machinery, particularly binding to miRNAs and AGO2, to promote embryonic stem cell proliferation by repressing CDKN1A expression and facilitating G1-S transition 1. TRIM71 is itself a let-7 miRNA target, representing an evolutionarily conserved regulatory relationship critical for normal development 1. In neural development, TRIM71 maintains neuroepithelial stem cell proliferation and prevents premature differentiation by positively regulating FGF signaling through SHCBP1 stabilization 2. TRIM71 also regulates miRNA biogenesis, binding to MIR29A hairpin to modulate its levels [UniProt]. Beyond development, TRIM71 is reactivated in hepatocellular carcinoma where it drives carcinogenesis through IGF2BP1-mediated mRNA stabilization of CEBPA, promoting serine/glycine metabolism 3, and enhances cochlear supporting cell regenerative potential 4. Mutations in TRIM71 cause congenital hydrocephalus and a novel neurodevelopmental syndrome (TADD) characterized by ventriculomegaly, developmental delay, and brain structural defects through disrupted neuroepithelial cell fate determination 25. Additionally, TRIM71 is essential for germ cell development, with deficiency causing male infertility 6.