STK3 (serine/threonine kinase 3) is a stress-activated, pro-apoptotic kinase that serves as a core component of the Hippo signaling pathway, a conserved regulator of organ size control and tumor suppression 1. Following caspase-cleavage, STK3 enters the nucleus to induce chr8 condensation and DNA fragmentation. Within the Hippo cascade, STK3 phosphorylates and activates LATS1/2 kinases, which subsequently phosphorylate and inactivate the YAP1 oncoprotein, preventing its nuclear translocation and suppressing genes promoting cell proliferation and survival 1. STK3 is required to repress proliferation of mature hepatocytes and inhibit tumor formation. Beyond canonical Hippo signaling, STK3 regulates centrosome disjunction through NEK2 phosphorylation and modulates mitophagy in adipocytes by regulating BNIP3, thereby controlling mitochondrial function and energy expenditure 2. In pancreatic cancer, STK3 methylation by PRMT5 at R461/R467 suppresses its autophosphorylation and kinase activity, inactivating Hippo signaling 3. Notably, in gastric cancer, STK3 functions as a YAP1 transcriptional target that activates Wnt/β-catenin signaling through GSK-3β phosphorylation, promoting stemness and chemoresistance 4. These context-dependent roles reveal STK3 as both a tumor suppressor and, under certain conditions, an oncogenic effector.