TET3 (tet methylcytosine dioxygenase 3) is a Fe²⁺ and α-ketoglutarate-dependent dioxygenase that catalyzes the sequential oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC), constituting the first step in active DNA demethylation 1. TET3 plays crucial roles in embryonic development, particularly during zygotic formation where it mediates paternal pronucleus demethylation while maternal chr2 remains protected 2. The enzyme exhibits preferential binding to CpG-rich regions and contributes to transcriptional regulation of developmental genes 3. TET3 functions through both enzymatic activity-dependent DNA demethylation and enzymatic activity-independent mechanisms, including recruitment of O-GlcNAc transferase OGT to promote histone modifications 4. Disease relevance includes Beck-Fahrner syndrome caused by TET3 deficiency, characterized by intellectual disability, developmental delay, hypotonia, and growth abnormalities 2. Additionally, TET3 insufficiency in oocytes contributes to maternal inheritance of glucose intolerance 5, while overexpression in macrophages promotes endometriosis 6. TET3 also regulates inflammatory responses in astrocytes following traumatic brain injury through epigenetic control of IRF1 expression 7, highlighting its broad clinical significance in development, metabolism, and neuroinflammation.