Inside Front Cover: Enzyme‐Activated Orthogonal Proteolysis Chimeras for Tumor Microenvironment‐Responsive Immunomodulation (Angew. Chem. Int. Ed. 22/2025)

Novel tumor microenvironment‐responsive enzyme‐activated clickable PROTACs, termed as ENCTACs, are presented by Bengang Xing et al. in their Research Article ( e202423057 ). Such ENCTACs enable selective formation of heterobifunctional degraders to disrupt BRD4 in tumor, effectively downregulating PD−L1 for immunotherapy. The cover illustration depicts fragments conjugation after enzyme reaction, realizing protein intervention and activating the antitumoral immune system.