For example, many ZBTB transcription factors, including ZBTB7A, ZBTB7B and ZBTB35, are required for the proliferation and differentiation of T cells (59,121); ZBTB7A is involved in tumorigenesis and pluripotency control through signaling pathways or chromatin remodelers (108,122,123); ZBTB7B drives brown fat development via long non-coding RNAs (111); ZBTB11 regulates neutrophil development, and its mutation causes intellectual disability (124,125); and ZBTB21 is associated with the pathogenesis of congenital heart defects in Down syndrome (126). Here, ZBTB21 is linked to Down syndrome.