Various mechanisms lead to NUMB LOF in BC: i) reduction in NUMB protein levels due its hyper‐degradation, as evidenced in a limited number of clinical cases;[1r] ii) alterations in NUMB splicing resulting in downregulation of exon 3‐containing isoforms that regulate p53;[1b] iii) aberrant NUMB phosphorylation leading to loss of its asymmetric partitioning and functional inactivation.[1e] The first mechanism, involving NUMB hyper‐degradation, has been associated with heightened ubiquitination,[1r] catalyzed by as yet uncharacterized molecular players. This evidence concerns the gene NUMB and breast cancer.