Emerging evidence for gene expression regulation and cell-fate determination via AGO(s) mediation has opened new windows for the mechanistic association of their functional-deregulation, gene-polymorphism, and protein-modification profiles with clinicο-pathological features leading to serious diseases such as viral infections, auto-immunities, cancers, metabolic dysfunctions, neuronal disorders, and infertilities. The gene discussed is FBXW7; the disease is cancer.