p38γ and p38δ MAP kinases in inflammation.

The p38γ and p38δ mitogen-activated protein kinases (MAPKs) are members of the p38 family that have emerged as important regulators of inflammatory signaling. Initially considered minor or alternative isoforms, accumulating evidence has revealed distinct and overlapping functions for p38γ and p38δ in innate immunity, tissue homeostasis, inflammatory disease, and cancer. These kinases regulate immune responses through diverse mechanisms controlling cytokine production, gene expression, immune-cell activation, and migration. In addition, recent studies suggest that some functions of p38γ and p38δ may occur independently of their catalytic activity, highlighting the complexity of their biological roles. The present review summarizes current knowledge of the molecular features, substrates, immune cell functions, and disease associations of p38γ and p38δ and discusses their potential as therapeutic targets while addressing the challenges associated with their pharmacological modulation.