MAPK12, also known as p38γ, is a serine/threonine kinase that serves as an essential component of the p38 MAPK signaling pathway, responding to cellular stress and inflammatory stimuli 1. This kinase plays critical roles in cancer biology, particularly in tumor progression and metastasis across multiple cancer types including gastrointestinal cancers and breast cancer 1 2. MAPK12 demonstrates oncogenic properties by promoting cell proliferation in thyroid carcinoma cells and serving as a negative prognostic marker in various cancers 2. In triple-negative breast cancer, MAPK12 drives cancer stem cell expansion and is transcriptionally regulated by G-quadruplex structures at its promoter, which can be therapeutically targeted 3. The protein also contributes to tumor microenvironment regulation, as targeting MAPK12 in cancer-associated fibroblasts reduces extracellular matrix production and enhances immunotherapy effectiveness 4. Additionally, MAPK12 is involved in chondrocyte senescence and osteoarthritis progression, where its downregulation exacerbates cartilage degradation 5. MAPK12 expression correlates with immune checkpoint markers and affects tumor immunotherapy sensitivity, making it a potential therapeutic target 2. The kinase also plays roles in prolactinoma development, where its inhibition shows anti-tumor effects 6.