This review summarizes developmental origins, differentiation protocols, and applications of human iPSC/ESC-derived microglia to model microglial biology and disease-relevant phenotypes in neurodegeneration.

Offers a human-relevant platform to study microglia-driven inflammation and genetics relevant to Parkinson's disease and to prioritize targets and screens for therapeutic development, though as a review it provides synthesis rather than new actionable experimental findings.

Neurodegenerative diseases are characterized by progressive neuronal dysfunction and loss. Microglia, the brain's resident macrophages, are key contributors to disease pathogenesis, with many genetic risk variants enriched in microglia-specific genes. While rodent models have provided valuable insights, human induced pluripotent stem cell (iPSC) and embryonic stem cell (ESC) technologies now enable the generation of human microglia-like cells, offering a physiologically relevant platform to study human microglial biology. This review discusses the developmental origins and functions of microglia, current differentiation approaches, and how these models help elucidate disease-relevant phenotypes and molecular mechanisms in neurodegeneration.