Aggressive breast cancers often resist standard therapies due to mechanisms related to both tumour cells and the tumour microenvironment. Many chemotherapeutic drugs increase ceramides, lipids that promote cell death. CERT, a protein involved in ceramide transport, reduces their accumulation; therefore, lowering CERT levels could increase sensitivity to chemotherapy by raising ceramide levels and improving the therapeutic response. This project investigates CERT’s role in treatment resistance and develops new degraders capable of directing CERT directly to the proteasome via Usp14, without relying on E3 ligases. The molecules developed have been validated through chemical synthesis, biochemical characterisation and studies in breast cancer models, providing evidence that CERT is a promising therapeutic target.