{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nProtein kinase D1 (PRKD1) is a multifunctional serine/threonine kinase whose dysregulation has been implicated in developmental disorders and cancer. Inherited or de novo mutations in PRKD1 have been linked to syndromic congenital heart defects, while hotspot mutations (such as p.Glu710Asp) act as oncogenic drivers in low‐grade adenocarcinomas of the salivary glands. In several epithelial tumors—including breast and prostate cancers—PRKD1 plays a key role in maintaining the epithelial phenotype by suppressing epithelial‐to‐mesenchymal transition, and its loss is associated with invasion and metastasis. Moreover, reviews and expression studies underscore PRKD1’s importance in mediating diverse cellular responses that influence tumor growth and androgen independence."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nPRKD1 is also central to the regulation of intracellular membrane dynamics and signal transduction. It is recruited to the trans‐Golgi network by binding diacylglycerol and contributes to the fission of transport carriers destined for the plasma membrane by phosphorylating substrates such as CERT and oxysterol‐binding protein (OSBP)—activities that are essential for the maintenance of lipid homeostasis and secretory transport. In addition, PRKD1 influences endothelial barrier function and angiogenesis downstream of vascular endothelial growth factor by modulating the phosphorylation and nuclear export of class IIa histone deacetylases and the stress protein HSP27. Methodological advances, including the development of substrate‐directed phospho‐specific antibodies, have facilitated identification of its targets and underscored its roles in regulated vesicle trafficking, autophagy via phosphorylation of Vps34, and even post‐Golgi cargo processing."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "23"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its roles in membrane trafficking, PRKD1 coordinates cytoskeletal dynamics and stress responses that impact cell motility, inflammation, and intercellular communication. Under oxidative and other stress conditions, PRKD1 is activated—often via sequential phosphorylation events involving Src/Abl and PKCδ—to stimulate NF-κB and CREB signaling and promote survival. It phosphorylates key regulators of the actin cytoskeleton including the cofilin phosphatase SSH1L and cortactin, thereby modulating actin severing and lamellipodia formation to fine-tune migration and invasion. Moreover, PRKD1 has been implicated in processes as diverse as integrin recycling, epithelial barrier regulation during viral infections, and the release of small extracellular vesicles in pancreatic cancer, further highlighting its integrative role in both normal physiology and disease."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "24", "end_ref": "39"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Johan Van Lint, An Rykx, Yusuke Maeda, et al. 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