MAPK signaling pathways are crucial for regulating various cellular functions, including proliferation, differentiation, apoptosis, survival, inflammation, and innate immunity. These pathways are composed of three hierarchical kinase components: MAP3K, MAP2K, and MAPK. Compromised MAPK signaling contributes to the pathogenesis of diverse human diseases, including cancer and neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. The JNK and p38 MAPK pathways are activated by various types of cellular stress and proinflammatory cytokines. The Ras-Raf-MEK-ERK pathway is involved in cancer development through cell proliferation and metastasis. The p38 MAPK pathway contributes to neuroinflammation and is associated with anticancer drug resistance. ERK1 and ERK2 are activated by MEK1 or 2, while ERK5 is activated by MEK5. MAPK signaling pathways are activated either through bimodular interactions between kinase components or by the formation of a signaling complex involving scaffold proteins. Scaffold proteins play a key role in the regulation of MAPK signaling pathways. This review summarizes recent research on the roles of MAPK signaling pathways in human diseases, with a focus on cancer and neurodegenerative conditions.MAPK signaling pathways are crucial for regulating various cellular functions, including proliferation, differentiation, apoptosis, survival, inflammation, and innate immunity. These pathways are composed of three hierarchical kinase components: MAP3K, MAP2K, and MAPK. Compromised MAPK signaling contributes to the pathogenesis of diverse human diseases, including cancer and neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. The JNK and p38 MAPK pathways are activated by various types of cellular stress and proinflammatory cytokines. The Ras-Raf-MEK-ERK pathway is involved in cancer development through cell proliferation and metastasis. The p38 MAPK pathway contributes to neuroinflammation and is associated with anticancer drug resistance. ERK1 and ERK2 are activated by MEK1 or 2, while ERK5 is activated by MEK5. MAPK signaling pathways are activated either through bimodular interactions between kinase components or by the formation of a signaling complex involving scaffold proteins. Scaffold proteins play a key role in the regulation of MAPK signaling pathways. This review summarizes recent research on the roles of MAPK signaling pathways in human diseases, with a focus on cancer and neurodegenerative conditions.