BioCentury reported innovators are converting extracellular targeted protein degraders (TACs) into bispecific formats that exploit membrane E3 ligases and novel lysosomal internalizing receptors. Developers are combining antibody engineering with lysosomal trafficking mechanisms to clear extracellular and membrane‑bound targets that traditional small‑molecule proteolysis approaches cannot reach. The landscape expansion includes multiple formats and new E3 targets, signaling a shift from intracellular ubiquitin‑proteasome mechanisms toward extracellular lysosomal routes. Companies will need to demonstrate targeted degradation, tolerability and clinical feasibility as they move bispecific TACs into IND‑enabling studies.