Abstract: In accordance with the purpose(s) of the present disclosure, as embodied and broadly described herein, the disclosure, in one aspect, relates to scaffold molecules having anti-hRPN13 activity, proteolysis targeting chimeras (PROTACs) incorporating the same, methods of making same, pharmaceutical compositions comprising same, and methods of treating cancers involving aberrant hRpn13 activity and/or the presence of hRpn13-Pru/hRpn13 or variants thereof using the same.