PDCD10 (Programmed Cell Death 10) is a critical regulator of cerebrovascular integrity and a key component of the STRIPAK (Striatin-Interacting Phosphatase and Kinase) complex. The protein promotes cell proliferation, modulates apoptotic pathways, and increases mitogen-activated protein kinase activity 1. PDCD10 is essential for maintaining blood-brain barrier integrity, with loss-of-function mutations causing cerebral cavernous malformations (CCMs), a genetic cerebrovascular disease characterized by abnormally packed blood vessels 2. Mechanistically, PDCD10 deficiency leads to disrupted endothelial signaling cascades, including upregulated mTORC1 signaling in brain endothelial progenitor cells 3 and altered caveolae-mediated Tie2 signaling pathways 4. The protein functions through both brain endothelial cells and gut epithelial cells, establishing a gut-brain axis where gut barrier dysfunction can exacerbate CCM formation 5. PDCD10 mutations result in earlier disease onset and more severe clinical manifestations compared to other CCM gene mutations 2. Loss of PDCD10 triggers pathophysiological gene expression patterns involving KLF2 signaling and promotes aberrant angiogenesis through astrocyte-mediated VEGF production 6. Therapeutic approaches targeting downstream pathways, including mTOR inhibition with rapamycin, show promise for treating CCM pathogenesis 3.