TET2 (tet methylcytosine dioxygenase 2) is a Fe2+ and α-ketoglutarate-dependent dioxygenase that catalyzes the oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) and subsequent derivatives, playing a crucial role in active DNA demethylation 1. The enzyme specifically recognizes CpG dinucleotides and shows substrate preference for 5mC in CpG contexts, with its catalytic cavity allowing accommodation of 5mC derivatives for iterative oxidation 1. Beyond its canonical demethylation function, TET2 regulates chr4 accessibility by oxidizing m5C in retrotransposon RNA, which prevents MBD6-mediated H2AK119ub deubiquitination and maintains chr4 in a more closed state 2. TET2 is essential for normal hematopoiesis, particularly myelopoiesis, and its loss leads to increased hematopoietic stem cell self-renewal and myeloid transformation 3. Loss-of-function mutations in TET2 are frequently observed in clonal hematopoiesis, myelodysplastic syndrome, and acute myeloid leukemia 4. TET2-deficient cells show resistance to inflammatory stress, contributing to their selective advantage during aging 5. Additionally, TET2 functions independently of its demethylase activity in vascular smooth muscle cells, forming inhibitory complexes with HDAC1/2 and SNIP1 to suppress osteogenic gene expression and prevent vascular calcification 6.