PRKD3 (protein kinase D3) is a serine/threonine kinase that plays multifaceted roles in cellular signaling and disease pathogenesis. The protein functions as an oncogenic driver in multiple cancer types, particularly breast and gastric cancers, where it promotes tumor cell proliferation, migration, and metabolic reprogramming 123. Mechanistically, PRKD3 activates key signaling pathways including ERK1/c-MYC in breast cancer and p65/PFKFB3-mediated glycolysis in gastric cancer 32. The kinase also regulates cell cycle progression through modulation of proteins like CDK1, CyclinB1, and CHK1 4. Beyond cancer, PRKD3 serves protective functions in liver homeostasis, where its deficiency promotes hepatic fibrosis through altered macrophage polarization and sustained STAT6 activation via decreased SH2-containing protein tyrosine phosphatase-1 activity 5. Genetic studies have implicated PRKD3 variants in cardiovascular disease risk, identifying it as a potential therapeutic target for heart failure prevention 6. Additionally, PRKD3 variants are associated with Alzheimer's disease risk 7. The protein's diverse functions across different tissues suggest context-dependent roles in maintaining cellular homeostasis versus promoting pathological processes.