<p>Microglia-mediated neuroinflammation is a pathological hallmark of various neurological diseases. Altered microglial states promote disease progression and induce an inflammatory microenvironment. Therapies aimed at modulating microglial signaling demonstrate certain therapeutic effects, yet their efficacy is limited in terms of durability and may sometimes have a double-edged impact. This is presumably because disease-associated microglial dysfunction stems from its multi-layered and self-reinforcing mechanisms. Microglia replacement therapy has emerged as an approach that first depletes resident microglia and then either directly transplants microglia or induces the repopulation/engraftment of microglia in the niche. This strategy shows therapeutic effects in pre-clinical models, but the intracellular mechanisms supporting its therapeutic durability remain unclear. In this review, we present a Golgi-centered, evidence-stratified perspective, proposing that Golgi homeostasis may represent a candidate organelle-level checkpoint for post-replacement microglial state stability. As a structural and signaling hub that integrates receptor maturation, innate immune signaling, lipid handling, and secretory competence, the Golgi apparatus provides a testable framework for understanding how intracellular organization may contribute to durable microglial recalibration after replacement. Direct evidence linking microglial replacement to Golgi homeostasis remains limited, and whether Golgi recovery contributes to therapeutic durability requires future validation.</p>