Fragile X syndrome (FXS), a heritable intellectual and autism spectrum disorder (ASD), results from the loss of Fragile X mental retardation protein (FMRP). This neurodevelopmental disease state exhibits neural circuit hyperconnectivity and hyperexcitability. Canonically, FMRP functions as an mRNA-binding translation suppressor, but recent findings have enormously expanded its proposed roles. Although connections between burgeoning FMRP functions remain unknown, recent advances have extended understanding of its involvement in RNA, channel, and protein binding that modulate calcium signaling, activity-dependent critical period development, and the excitation–inhibition (E/I) neural circuitry balance. In this review, we contextualize 3 years of FXS model research. Future directions extrapolated from recent advances focus on discovering links between FMRP roles to determine whether FMRP has a multitude of unrelated functions or whether combinatorial mechanisms can explain its multifaceted existence.

脆性 X 综合征 (FXS) 是一种遗传性智力障碍和自闭症谱系障碍 (ASD)，是由脆性 X 智力迟钝蛋白 (FMRP) 缺失引起的。这种神经发育疾病状态表现出神经回路过度连接和过度兴奋。通常，FMRP 作为 mRNA 结合翻译抑制因子发挥作用，但最近的研究结果极大地扩展了其拟议的作用。尽管新兴的 FMRP 功能之间的联系仍然未知，但最近的进展加深了人们对其参与调节钙信号传导、活动依赖性关键期发育和兴奋-抑制 (E/I) 神经回路平衡的 RNA、通道和蛋白质结合的了解。 。在这篇综述中，我们回顾了 3 年的 FXS 模型研究。从最近的进展中推断出的未来方向侧重于发现 FMRP 角色之间的联系，以确定 FMRP 是否具有多种不相关的功能，或者组合机制是否可以解释其多方面的存在。