Based on this, Rao Yu’s research group, Zhu Jun’s research group, and Liu Wan Li’s research group worked together to successfully and efficiently degrade a variety of clinically relevant mutant BTK proteins by constructing a novel high solubility BTK protein degradation agent PROTAC 25 (Table 1) and overcomes the clinical resistance of B-cell lymphoma (BCL) to the clinical first-line drug ibrutinib caused by BTK protein mutation. The gene discussed is BTK; the disease is B-cell non-Hodgkin lymphoma.