MAPK1 (mitogen-activated protein kinase 1) is a serine/threonine kinase that functions as a central hub in the MAPK signaling cascade 1. Beyond its well-characterized kinase activity, MAPK1 regulates diverse cellular processes including mitochondrial homeostasis, lipid metabolism, and fibrotic responses. Mechanistically, MAPK1 phosphorylates multiple substrates: it phosphorylates ULK1 to trigger its ubiquitination and degradation, attenuating mitophagy 1; phosphorylates ME1 at T103 to enhance lipogenesis 2; and increases expression of MAPK1 itself, disrupting mitochondria-associated ER membranes (MAMs) via PACS-2 downregulation 3. MAPK1 also participates in fibrotic signaling alongside FYN and PTK2 in hepatic stellate cells 4. Disease relevance includes breast cancer bone metastasis, where elevated MAPK1 kinase activity drives mitophagy defects and NLRP3 inflammasome activation 1; colorectal carcinogenesis through lipid metabolism enhancement 2; diabetic kidney disease via MAM disruption and mitochondrial fragmentation 3; and bladder cancer progression through the circPSMA7/miR-128-3p/MAPK1 axis 5. Clinical significance is demonstrated by MEK/MAPK inhibitors (trametinib, PD0325901) showing therapeutic potential in MAPK1-dependent cancers, particularly those with elevated kinase activity 16.