Mapk15, also known as Mitogen Activated Protein Kinase 15, is an atypical member of the MAP kinase family. It plays essential roles in multiple cellular processes. It is involved in pathways related to oxidative stress response, autophagy, and Hedgehog signaling, which are crucial for maintaining cellular homeostasis, development, and disease prevention [1-4, 8-10].

In terms of oxidative stress, reduced Mapk15 expression in cells led to decreased mitochondrial respiration, increased mitochondrial ROS levels, and accumulation of nuclear DNA damage, resulting in senescence, indicating its importance in protecting cells from oxidative stress-dependent cellular senescence [1]. In airway epithelial cells of COPD patients, cigarette smoke activated the Mapk15-ULK1 signaling pathway, promoting mitophagy and mitochondrial oxidative stress [2]. In medulloblastoma cells, inhibition of Mapk15 signaling disrupted oncogenic Hedgehog overactivation in a cilia-dependent manner, preventing cell proliferation [3].

In conclusion, Mapk15 is a key regulator in controlling oxidative stress responses, autophagy, and Hedgehog signaling. Its dysregulation is associated with various diseases such as age-associated diseases, COPD, and medulloblastoma. Research on Mapk15 using gene-knockout models has provided valuable insights into the underlying molecular mechanisms of these diseases, potentially paving the way for novel therapeutic strategies.