Wang et al. (2024) shed light on a novel mechanism involving circ-PPID (peptidylprolyl isomerase D circular RNA) in sensitizing breast cancer cells to trastuzumab treatment by modulating HER2 ac4C modification. Circ-PPID was found to reduce HER2 mRNA ac4C levels by binding to NAT10, thereby enhancing the efficacy of trastuzab. These findings provide valuable insights into the role of ac4C modifications in breast cancer development and drug resistance. The gene discussed is ERBB2; the disease is breast carcinoma.