PRKD2 is a serine/threonine kinase that translates diacylglycerol signals into prolonged cellular responses, functioning as a critical regulator of immune activation, cell proliferation, and metabolic homeostasis. Mechanistically, PRKD2 activates MAPK1/3 (ERK1/2) signaling and NF-κB pathways in response to various stimuli, including T-cell receptor engagement and oxidative stress 1. In T-cell biology, PRKD2 interacts with LCK to activate NFAT transcription factors and regulate IL-2 production, while also controlling T follicular helper cell differentiation through mutual inhibition with Bcl6 to constrain excessive antibody production 23. Beyond immunity, PRKD2 regulates Golgi membrane trafficking, angiogenesis through VEGFA signaling, and cell adhesion 45. Disease relevance includes multiple myeloma, where PRKD2 upregulation drives tumor stemness and immune evasion while conferring vulnerability to VEGFR/PDGFR inhibitors 6. PRKD2 mutations associate with chemotherapy resistance in cervical cancer 7, primary sclerosing cholangitis susceptibility 8, abdominal aortic aneurysm risk 9, and metabolic dysfunction; PRKD2 deficiency causes hyperinsulinemia and insulin resistance 10. Clinically, PRKD2 represents a promising therapeutic target across malignancies, metabolic disease, and inflammatory conditions.