These substrates are critical for tumor cells, as XPO1 cargos are involved in the majority of hallmarks of cancer: sustained proliferation (c-ABL, c-Myc, c-Met, EGFR), evading growth suppressors (p21, p27), genome instability (p53, DNA topoisomerases), resisting cell death (survivin, Bok, FOXO), enabling replicative immortality (TERT), inducing angiogenesis (Fbw7, COMMD1), activating invasion and metastasis (FBXL5, snail, APC, c-Pml), deregulating cellular energetics (eIF4E), and tumor-promoting inflammation (Cox-2) [5,11,35]. The gene discussed is FBXL5; the disease is neoplasm.