TET1 (tet methylcytosine dioxygenase 1) is a 2-oxoglutarate- and Fe(II)-dependent dioxygenase that catalyzes conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), playing a central role in active DNA demethylation 1. This epigenetic modification disinhibits gene silencing, allowing TET1 to regulate transcription of specific genes 2. TET1 exhibits isoform-specific functions: while isoform 1 targets CpG-rich promoters for global demethylation, isoform 2 localizes to replication sites during S phase, promoting heterochromatic 5hmC formation and regulating distinct neuronal genes 3. TET1 demonstrates critical roles across multiple biological contexts. In immune regulation, NAD+ metabolism maintains TET1 activity to facilitate IFNγ-induced Irf1 demethylation, driving PD-L1 expression and tumor immune evasion 4. In germ cell development, TET1-mediated active demethylation is essential for epigenetic reprogramming of pluripotent stem cell-derived PGCLCs into functional germ cells; TET1 deficiency causes differentiation into extraembryonic lineages and failure to activate spermatogenesis/oogenesis genes 5. TET1 also coordinates with RNA m6A modifications through YTHDC2 to regulate transposable element activity in embryonic stem cells 6. In disease contexts, TET1 promotes airway smooth muscle proliferation in asthma via nestin-mTOR pathway activation 2, while TET1 depletion reduces M1 macrophage polarization through NF-κB inhibition 7. These findings establish TET1 as a versatile epigenetic regulator with therapeutic potential in immunotherapy and developmental diseases.