Organelle-anchored translation factories: the roles of neuronal RNA-binding protein condensates in organizing local protein synthesis in neurological diseases

Abstract

Abstract Neurons face a fundamental proteostasis challenge: synapses and axons located far from the soma must rapidly remodel their proteome during activity, stress, and development. While local protein synthesis has long been recognized as essential for meeting these demands, classical models largely focused on ribonucleoprotein granules as autonomous carriers of translationally silent mRNAs, treating membranous organelles as parallel logistics or metabolic systems. Recent work overturns this view, revealing that endosomes, lysosomes, axonal endoplasmic reticulum, mitochondria, and their contact sites actively function as mobile translation platforms. In this review, we propose an RBP-centered framework in which phase-separated condensates physically tether specific mRNA cohorts to organelle surfaces, coupling mRNA transport, translational control, and organelle dynamics into a unified network. By organizing recent discoveries into functional modules—long-range transport, localized translation, and stress buffering—this neuron-focused framework identifies organelle-anchored translation factories as a unifying principle of synaptic proteostasis and a broadly applicable design paradigm for highly polarized cells. Keywords RNA-binding proteins, ribonucleoprotein granules, neuronal local translation, organelle-anchored translation