In sum, our comprehensive studies in mouse models and human samples support that Rank-expressing microglia are key regulators of microglia activation, GnRH neuron functionality and, in turn, sexual development and fertility, uncovering RANK as a potential therapeutic target in endocrine disorders and fertility syndromes, as well as a candidate gene for molecular diagnosis of CHH disorder. Here, TNFRSF11A is linked to endocrine system disorder.