TET enzymes play a critical role in DNA methylation, development, and cancer. They oxidize 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC), facilitating active DNA demethylation. TET2 is frequently mutated in hematological malignancies, and its disruption is an early event in disease onset. TET proteins regulate DNA methylation and transcription, and their activity is essential for normal development and preventing cellular transformation. TET enzymes are multidomain proteins with a conserved double-stranded β-helix (DSBH) domain, a cysteine-rich domain, and binding sites for Fe(II) and 2-oxoglutarate (2-OG). TET1 and TET3 have an N-terminal CXXC zinc finger domain that binds DNA. TET-mediated oxidation of 5mC leads to the formation of 5hmC, 5fC, and 5caC, which can be recognized and excised by TDG and the base excision repair (BER) pathway, resulting in DNA demethylation. 5hmC can also promote passive DNA demethylation, while 5fC and 5caC are primarily involved in active demethylation. TET proteins have dual roles in DNA methylation regulation: they can stall after initial oxidation of 5mC to 5hmC, maintaining stable 5hmC levels, or proceed to further oxidation to 5fC and 5caC, leading to net DNA demethylation. TET proteins are involved in various biological processes, including embryonic development, hematopoiesis, and immune responses. TET2 mutations are associated with hematological malignancies, and their loss leads to increased DNA methylation and impaired differentiation. TET2 mutations are found in various hematological diseases, including myeloid and lymphoid malignancies, and are linked to clonal hematopoiesis and cancer predisposition. TET2 disruption in mouse models increases HSC proliferation but rarely leads to malignant transformation, suggesting that additional oncogenic events are required for disease development. TET proteins are essential for maintaining DNA methylation patterns and preventing aberrant methylation, and their dysfunction contributes to cancer progression.TET enzymes play a critical role in DNA methylation, development, and cancer. They oxidize 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC), facilitating active DNA demethylation. TET2 is frequently mutated in hematological malignancies, and its disruption is an early event in disease onset. TET proteins regulate DNA methylation and transcription, and their activity is essential for normal development and preventing cellular transformation. TET enzymes are multidomain proteins with a conserved double-stranded β-helix (DSBH) domain, a cysteine-rich domain, and binding sites for Fe(II) and 2-oxoglutarate (2-OG). TET1 and TET3 have an N-terminal CXXC zinc finger domain that binds DNA. TET-mediated oxidation of 5mC leads to the formation of 5hmC, 5fC, and 5caC, which can be recognized and excised by TDG and the base excision repair (BER) pathway, resulting in DNA demethylation. 5hmC can also promote passive DNA demethylation, while 5fC and 5caC are primarily involved in active demethylation. TET proteins have dual roles in DNA methylation regulation: they can stall after initial oxidation of 5mC to 5hmC, maintaining stable 5hmC levels, or proceed to further oxidation to 5fC and 5caC, leading to net DNA demethylation. TET proteins are involved in various biological processes, including embryonic development, hematopoiesis, and immune responses. TET2 mutations are associated with hematological malignancies, and their loss leads to increased DNA methylation and impaired differentiation. TET2 mutations are found in various hematological diseases, including myeloid and lymphoid malignancies, and are linked to clonal hematopoiesis and cancer predisposition. TET2 disruption in mouse models increases HSC proliferation but rarely leads to malignant transformation, suggesting that additional oncogenic events are required for disease development. TET proteins are essential for maintaining DNA methylation patterns and preventing aberrant methylation, and their dysfunction contributes to cancer progression.