Despite that HMGA2 is a nuclear protein that does not contain Signal Peptide (SP) (Keller et al. 2008), the truncated form of HMGA2 protein—associated with tumor aggressiveness—is present in the cytoplasm in addition to the nucleus (Campbell et al. 2023), as well as the phosphorylation occurring on both sides of the Nuclear Localization Signal (NLS) presented in the second AT-hook may facilitate the change of the HMGA2 localization from the nucleus to the cytoplasm, which facilitate its secretion by an independent-endoplasmic reticulum/Golgi pathway (Cattaruzzi et al. 2007). The gene discussed is HMGA2; the disease is neoplasm.