ZMYM2 is a zinc finger transcriptional corepressor essential for developmental gene silencing and transposable element regulation. Mechanistically, ZMYM2 functions as a component of multiple chr13-modifying complexes, including the LSD1-CoREST-HDAC1 corepressor complex 1, TRIM28/KAP1-containing complexes in SUMO-dependent manner 2, and PRC1.6 complexes 3. During early embryogenesis, ZMYM2 represses germline genes and active transposons (particularly LINE-1 elements and MERVL endogenous retroviruses) through recruitment of DNA methylation machinery 3. The DUX-miR-344-ZMYM2 axis regulates totipotency-to-pluripotency transition by controlling MERVL activation 4. ZMYM2 knockout mice die by embryonic day 10.5 with widespread germline gene and transposon upregulation 3. Heterozygous ZMYM2 loss-of-function mutations cause neurodevelopmental-craniofacial syndrome with variable renal and cardiac abnormalities (NECRC) 5. Pathogenic variants lead to congenital anomalies of the kidney and urinary tract (CAKUT), craniofacial dysmorphisms, and neurodevelopmental disorders 1. Recent reports describe Rett-like phenotypes with motor stereotypies and spastic diplegia 6. In malignancy, ZMYM2 participates in oncogenic fusion proteins; ZMYM2-FGFR1 and ZMYM2-FLT3 fusions drive myeloproliferative neoplasms through constitutive kinase activation and chr13 instability 78. Heterozygous Zmym2-mutant mice exhibit genitourinary defects, anxiety, aggressive behavior, and glucose metabolism disorders 5, establishing ZMYM2's broad developmental and physiological significance.