Pdcd10, also known as CCM3, was initially identified as an apoptosis-related gene. It is a key gene as mutations in it cause cerebral cavernous malformation (CCM), a neurovascular disease [1]. The Pdcd10/CCM3 protein has multiple subcellular localizations, interacts with several multi-protein complexes and signaling pathways, and thus governs many cellular functions such as cell-to-cell junctions, cytoskeleton organization, cell proliferation, apoptosis, exocytosis, and angiogenesis [1].

In kidney tubules, Pdcd10-deficient mice developed polyuria. The levels of total and phosphorylated aquaporin 2 (Aqp2) protein in the apical membrane of tubular epithelial cells were decreased, along with increased expression and membrane targeting of Ezrin and phosphorylated Ezrin, Radixin, Moesin (p-ERM) proteins and impaired intracellular vesicle trafficking. This identified the PDCD10-STK-ERM signaling pathway as important for water balance control in the kidneys [2]. In glioblastoma cells, knockdown of Pdcd10 led to increased chemo-resistance to temozolomide (TMZ), promoted tumor cell regrowth, upregulated MGMT and DNA mismatch repair genes, and caused dedifferentiation of glioblastoma cells, highlighting its role in tumor suppression related to chemo-resistance and dedifferentiation [3].

In conclusion, Pdcd10 is crucial for maintaining cellular homeostasis, with its functions extending across various cellular processes. Studies using Pdcd10-deficient mouse models have revealed its significance in diseases like CCM, kidney water balance regulation, and cancer. These models have provided insights into the molecular mechanisms underlying these disease conditions, contributing to our understanding of Pdcd10's role in health and disease.