Nupr1 is a small, highly basic and loosely folded multifunctional protein whose expression is induced by several stresses. Its relation to cancer was first suggested by its overexpression in several human malignancies and the association of its expression with breast cancer metastasis. Accordingly, Nupr1 is structurally related to the high-mobility group (HMG) of transcriptional regulators, which play a key role in the stress response and in cancer progression. Nupr1 interacts with numerous partners to regulate cell cycle, programmed cell death, autophagy, chromatin accessibility, and transcription, and its expression is required for regulation of TGFβ activity. Pleiotropic functions accomplished by Nupr1 depend on its molecular partners, its location into the cell, its expression level and on the cell-type. Nupr1 might be a new drug-targetable protein whose blockade would prevent cancer progression and metastasis development. J. Cell. Physiol. 226: 1439–1443, 2011. © 2010 Wiley-Liss, Inc.