It has been shown that the E3 ligases RNF181 and RNF31 can stabilize estrogen receptor α (ERα) and influence breast cancer progression.[11, 16] Meanwhile, other E3 ligases such as TRIM56 promote K63–linked polyubiquitination, which stabilizes ERα and fosters tamoxifen resistance.[17] Conversely, counter–regulatory DUBs, including OTUD7B and USP36, regulate ERα degradation by editing ubiquitin chains.[18, 19] These findings highlight the critical need to elucidate ERα regulatory networks, particularly at post‐translational levels. This evidence concerns the gene ESR1 and breast carcinoma.