Mapk15, also known as an atypical member of the MAP kinase family, plays crucial roles in multiple biological processes. It is involved in regulating cellular responses to oxidative stress, autophagy, and mitochondrial quality control. Through its association with pathways like NRF2-antioxidant response pathway, MAPK15 contributes to maintaining cellular homeostasis and is of great biological importance in understanding disease mechanisms [1,2].

In terms of specific functions, reduced Mapk15 expression in primary human airway epithelial cells led to decreased mitochondrial respiration, increased mitochondrial ROS levels, and ultimately cellular senescence, highlighting its role in protecting from oxidative stress-dependent senescence by inducing mitophagy [2]. In chronic obstructive pulmonary disease (COPD), cigarette smoke-activated Mapk15-ULK1 signaling promoted mitophagy and mitochondrial oxidative stress in airway epithelial cells, suggesting it as a potential therapeutic target [3]. In medulloblastoma cells, Mapk15 regulated Hedgehog signaling by controlling primary ciliogenesis, and its pharmacological inhibition prevented cell proliferation [4].

In conclusion, Mapk15 is essential for regulating cellular responses to oxidative stress, autophagy, and mitophagy, which are relevant to various diseases such as age-associated diseases, COPD, and medulloblastoma. Model-based research, including studies with reduced Mapk15 expression, has revealed its key roles in these biological processes and disease conditions, offering potential for novel therapeutic strategies.