MAPK15 is an atypical mitogen-activated protein kinase that regulates diverse cellular processes through both kinase-dependent and independent mechanisms. The protein plays a crucial role in autophagy regulation by interacting with LC3-family proteins and controlling mitophagy to maintain mitochondrial quality and prevent oxidative stress-induced cellular senescence 1. MAPK15 also regulates primary cilium formation and localization of ciliary proteins, localizing to basal body subdomains and controlling ciliogenesis across species 2. In oxidative stress responses, MAPK15 controls NRF2 activity by promoting its nuclear translocation and phosphorylation, thereby upregulating antioxidant gene expression 3. The kinase demonstrates oncogenic properties in various cancers, including chr8 myeloid leukemia where it mediates BCR-ABL1-induced autophagy and promotes cell proliferation 4, and gastric cancer where copy number gains contribute to c-Jun stability and malignant transformation 5. Conversely, in clear cell renal carcinoma, EGR1-mediated downregulation of MAPK15 inhibits proliferation and metastasis 6. Recent studies also implicate MAPK15 in environmental carcinogen responses, as PFOA exposure enhances MAPK15 expression through m6A modification, promoting prostate cancer progression 7. These diverse functions establish MAPK15 as a potential therapeutic target across multiple disease contexts.