The multifaceted PDCD10/CCM3 gene

The programmed cell death 10 (PDCD10) gene was originally identified as an apoptosis-related gene, although it is now usually known as CCM3, as the third causative gene of cerebral cavernous malformation (CCM). CCM is a neurovascular disease that is characterized by vascular malformations and is associated with headaches, seizures, focal neurological deficits, and cerebral hemorrhage. The PDCD10/CCM3 protein has multiple subcellular localizations and interacts with several multi-protein complexes and signaling pathways. Thus PDCD10/CCM3 governs many cellular functions, which include cell-to-cell junctions and cytoskeleton organization, cell proliferation and apoptosis, and exocytosis and angiogenesis. Given its central role in the maintenance of homeostasis of the cell, dysregulation of PDCD10/CCM3 can result in a wide range of altered cell functions. This can lead to severe diseases, including CCM, cognitive disability, and several types of cancers. Here, we review the multifaceted roles of PDCD10/CCM3 in physiology and pathology, with a focus on its functions beyond CCM.