The 26S proteasome recognizes substrates via ubiquitin receptors, a mechanism we leveraged to develop a small molecule ligand- and ubiquitination-independent targeted protein degradation strategy. Our proteasome-targeting chimera, Prote-a-Tac, links a proteasomal Ub receptor (PSMD4 or ADRM1) with a target-specific antibody fragment (such as a scFv or nanobody), allowing it to integrate into the proteasome and promote ubiquitin-independent degradation. The Prote-a-Tac platform demonstrated high specificity and minimal off-target effects, as confirmed by quantitative mass spectrometry.