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Retrotransposon Gag-like (RTL) genes play a variety of essential and important roles in the eutherian placenta and brain. It has recently been demonstrated that <i>RTL5</i> and <i>RTL6</i> (also known as <i>sushi-ichi retrotransposon homolog 8</i> (<i>SIRH8</i>) and <i>SIRH3</i>) are microglial genes that play important roles in the brain’s innate immunity against viruses and bacteria through their removal of double-stranded RNA and lipopolysaccharide, respectively. In this work, we addressed the function of <i>RTL9</i> (also known as <i>SIRH10</i>). Using knock-in mice that produce RTL9-mCherry fusion protein, we examined RTL9 expression in the brain and its reaction to fungal zymosan. Here, we demonstrate that <i>RTL9</i> plays an important role, degrading zymosan in the brain. The RTL9 protein is localized in the microglial lysosomes where incorporated zymosan is digested. Furthermore, in <i>Rtl9</i> knockout mice expressing RTL9ΔC protein lacking the C-terminus retroviral GAG-like region, the zymosan degrading activity was lost. Thus, RTL9 is essentially engaged in this reaction, presumably via its GAG-like region. Together with our previous study, this result highlights the importance of three retrovirus-derived microglial RTL genes as eutherian-specific constituents of the current brain innate immune system: <i>RTL9</i>, <i>RTL5</i> and <i>RTL6</i>, responding to fungi, viruses and bacteria, respectively.