The p38 MAP kinase pathway plays a crucial role in signal transduction and is involved in various biological processes. This review highlights the characteristics and components of the p38 pathway, including its activation mechanisms and downstream effects. The p38 kinases (p38α, p38β, p38γ, and p38δ) are activated by upstream kinases such as MKK3 and MKK6, and can be regulated by different upstream regulators. The pathway is activated in response to a wide range of extracellular stimuli, including inflammatory cytokines, growth factors, and stress conditions. p38 activation can be controlled through specific regulators and co-activated by various combinations of upstream regulators. The downstream substrates of p38 include protein kinases, transcription factors, and other cellular components, which mediate various cellular responses. p38 has been linked to inflammation, cell cycle regulation, apoptosis, development, cell differentiation, senescence, and tumorigenesis. The review also discusses the role of p38 in specific cell types and the complex regulation of the p38 pathway, emphasizing the importance of understanding its function in different contexts.The p38 MAP kinase pathway plays a crucial role in signal transduction and is involved in various biological processes. This review highlights the characteristics and components of the p38 pathway, including its activation mechanisms and downstream effects. The p38 kinases (p38α, p38β, p38γ, and p38δ) are activated by upstream kinases such as MKK3 and MKK6, and can be regulated by different upstream regulators. The pathway is activated in response to a wide range of extracellular stimuli, including inflammatory cytokines, growth factors, and stress conditions. p38 activation can be controlled through specific regulators and co-activated by various combinations of upstream regulators. The downstream substrates of p38 include protein kinases, transcription factors, and other cellular components, which mediate various cellular responses. p38 has been linked to inflammation, cell cycle regulation, apoptosis, development, cell differentiation, senescence, and tumorigenesis. The review also discusses the role of p38 in specific cell types and the complex regulation of the p38 pathway, emphasizing the importance of understanding its function in different contexts.