ESRRB (estrogen-related receptor beta) is an orphan nuclear receptor transcription factor that binds canonical estrogen-related receptor elements (ERREs) with the sequence 5'TCAAGGTCA-3' in gene promoters and enhancers 1. It functions as a key regulator of pluripotency and stem cell self-renewal, playing critical roles during early embryonic development and in pluripotent stem cell populations 2. ESRRB also acts as a mitotic bookmarking factor and regulates cellular metabolism to maintain pluripotent stem cell identity 2. In naive pluripotent states, ESRRB cooperates with transposable element-derived MIR enhancers to regulate pluripotency genes through 3D chr14 interactions 3. Beyond development, ESRRB has emerged as a critical oncogenic factor. In cervical cancer, ESRRB drives cell proliferation by activating SMAD7 transcription, inhibiting TGFβ signaling and promoting cell-cycle progression through a positive feedback loop with MYC 4. In acute lymphoblastic leukemia (ALL), ESRRB cooperates with glucocorticoid receptor (GR) to mediate glucocorticoid gene expression; ESRRB knockdown induces GC resistance, while ESRRB agonists enhance GC sensitivity 1. Additionally, TMBPF exposure induces ovarian granulosa cell senescence through ESRRB/p21 signaling upregulation 5. Clinically, ESRRB variants are associated with autosomal recessive deafness (DFNB35) and represent a novel candidate gene for inherited retinal diseases 6. ESRRB is also implicated in Meniere's disease genetic architecture through rare variants 7.