PKN3 is a serine-threonine kinase of the AGC family that serves as a critical regulator of cellular signaling and cytoskeletal dynamics 1. It integrates signals from multiple pathways including PI3K/PTEN and Wnt5a/Ror2, modulating cell migration, angiogenesis, and gene expression through interactions with Rho GTPases 1. In normal endothelial cells, PKN3 maintains cell morphology, junction integrity, and actin organization; knockdown impairs adherens junction dynamics and attenuates pro-inflammatory activation 2. PKN3 interacts directly with p130Cas adaptor protein via its polyproline sequence, promoting cancer cell growth and invasiveness independent of Src transformation 3. Pathologically, PKN3 is notably overexpressed in prostate and breast cancers, where loss-of-function studies demonstrate its essential role in driving tumor growth and metastasis 1. In trophoblasts, ANP enhances PKN3 expression through autophagy inhibition, promoting cell invasion via NFYA-mediated transcriptional regulation 4. Clinically, PKN3 represents a promising therapeutic target; RNAi-based approaches using PKN3 shRNA delivered via lipid nanoparticles achieved 60-65% tumor suppression in breast and prostate cancer models 56. Small-molecule kinase inhibitors targeting PKN3 have been identified and validated through phosphoproteomics 7.