Lysosomes serve as the primary degradation compartment within cells , capable of breaking down a wide range of biomolecules . This functionality has been harnessed for protein degradation using antibodies, such as LYTACs (lysosome-targeting chimeras) bispecific aptamer chimeras , and small molecules with approaches such as MrTACs (methylarginine targeting chimeras) . These methods all employ ligands or chemical tags to direct proteins to the lysosome for degradation. Inspired by these strategies, we investigated whether lysosomal trafficking could be exploited for targeted mRNA degradation. For this purpose, we utilized ispinesib, a small molecule originally developed to inhibit the mitotic kinesin Eg5 protein as an anti-cancer drug . Ispinesib has also been employed as a warhead in bi-functional molecules designed to degrade target proteins via lysosomal trafficking . The proposed mechanism for these bi-functional molecules involves LC3binding within the autophagosome, which subsequently fuses with the lysosome to mediate protein degradation. This activity was lost in the presence of inhibitors targeting various steps of autophagy or lysosomal trafficking. Bi-functionals with this mode of action are named as autophagosome-tethering compounds (ATTECs) .