In this review article, we discuss 5 aberrant contextual determinants of nucleocytoplasmic shuttling—PSPC1, TGIF1, NPM, Mortalin and EBP50—meeting these criteria and note their detailed mechanisms of action as oncogenic nucleocytoplasmic shuttling switches, potential use as biomarkers for stratification of cancer patients, and possibilities as putative therapeutic agents to potentially improve cancer therapy (Fig. 1; Table 1). The gene discussed is NHERF1; the disease is cancer.