The interaction between FBXW7 and NICD, as well as the subsequent regulation of NICD stability, are critical for several key cellular processes, such as the determination of cell fate, homeostasis, cell differentiation, and proliferation (for review, see Kar et al. 2021), and have been shown to be disturbed in several cancer types; e.g., T-ALL, melanoma, breast cancer, salivary gland cancer, and colon cancer (for review, see Kar et al. 2021). The gene discussed is FBXW7; the disease is breast cancer.