Nearly forty years of research dedicated to understanding the link between HTLV-1 and ATLL have consolidated the crucial roles of Tax-1 and HBZ in altering multiple pathways that govern cell proliferation, senescence and death, with the deregulation of NF-κB representing a hub, and miRNAs acting as fine-tuners of target gene expression. The gene discussed is HBZ; the disease is adult T-cell leukemia/lymphoma.