NUMB and cancer: By acting as neutral lipid storage depots, lipid droplets are important for lipid metabolism, including storing excessive neutral lipids or metabolizing them for energy.[7, 18] Lipid droplet homeostasis is associated with numerous diseases, including cancer progression.[25] Recent studies show that lipid droplets also mediate lipid protein degradation by the ubiquitin‐proteasome for quality and quantity control.[7, 18] In this study, we discovered that lipid droplets manipulate cell signaling by degrading Numb, an important non‐lipid droplet protein.