IL-34 is a pleiotropic cytokine that functions as a key regulator of myeloid cell development and immune homeostasis. Structurally, IL-34 serves as a ligand for the colony-stimulating factor-1 receptor (CSF-1R), activating downstream signaling cascades including MAPK/ERK phosphorylation 1. Primary functions include promoting proliferation, survival, and differentiation of monocytes and macrophages 1, while also regulating osteoclast development and bone resorption. IL-34 is essential for generating specialized macrophage populations, including brain microglia, Langerhans cells, and Paneth cells 1. The cytokine orchestrates both homeostatic and pathological immune responses by modulating macrophage polarization and chemotaxis through NF-κB-dependent CCL2 signaling 2. Clinically, IL-34 dysregulation contributes to multiple disease states. In cancer, IL-34 secretion by cancer stem cells drives M2-like macrophage polarization and immunosuppression in p53-inactivated tumors, promoting immune escape and poor prognosis 3. IL-34 blockade synergizes with anti-PD-1 therapy 3. In cardiac ischemia-reperfusion injury, elevated IL-34 exacerbates myocardial damage through macrophage recruitment and pathological polarization 2. IL-34 is also implicated in ischemic stroke pathophysiology 4 and canine atopic dermatitis, where increased serum levels correlate with inflammatory disease 5. These findings position IL-34 as a therapeutic target across inflammatory, neoplastic, and cardiovascular diseases.