Knockdown of UBA6 abolished the squamocin‐mediated ubiquitination and degradation of both EZH2 and MYC (Figure 6C,D), while silencing UBA1 had minimal impact (Figure S6B, Supporting Information), suggesting that squamocin activates the UPS via UBA6 rather than UBA1 in HNSCC. Here, UBA6 is linked to head and neck squamous cell carcinoma.