Abstract

Over the last decade, our appreciation of the importance of the nucleolus for cellular function has progressed from the ordinary to the extraordinary. We no longer think of the nucleolus as simply the site of ribosome production, or a dynamic subnuclear body noted by pathologists for its changes in size and shape with malignancy. Instead, the nucleolus has emerged as a key controller of many cellular processes that are fundamental to normal cell homeostasis and the target for dysregulation in many human diseases; in some cases, independent of its functions in ribosome biogenesis. These extra‐nucleolar or new functions, which we term “non‐canonical” to distinguish them from the more traditional role of the nucleolus in ribosome synthesis, are the focus of this review. In particular, we explore how these non‐canonical functions may provide novel insights into human disease and in some cases new targets for therapeutic development.