IL-24 is a multifunctional cytokine produced primarily by epithelial cells and T cells that plays distinct roles in tissue repair, immune regulation, and inflammation. 1 IL-24 is predominantly induced by barrier epithelial progenitors following tissue injury, independent of pathogen exposure, and is essential for epidermal proliferation, re-epithelialization, and dermal wound regeneration through autocrine and paracrine signaling involving JAK-STAT3 and metabolic pathways. 2 As an IL-10 family member, IL-24 maintains epithelial tissue homeostasis and facilitates tissue healing during infectious and inflammatory injuries. IL-24 signals through heterodimeric receptor complexes (IL20RA/IL20RB or IL20RB/IL22RA1) to activate JAK1-STAT3 and MAPK pathways, promoting pro-inflammatory mediator secretion. 3 In Th17 cells, IL-17A triggers autocrine IL-24 induction, which negatively regulates pathogenic Th17 cytokine production, providing an intrinsic regulatory mechanism. Disease relevance is substantial: IL-24 elevation contributes to pulmonary fibrosis progression through macrophage M2 polarization, 4 atopic dermatitis via IL-33-mediated type 2 immunity, 5 psoriasis through inflammatory fibroblast activation, 6 and esophageal cancer metastasis via tumor microenvironment remodeling. 7 Clinically, IL-24 represents a potential therapeutic target for inflammatory and fibrotic diseases.