Abstract

The precise regulation of protein organization within presynaptic nerve terminals is critical for efficient neurotransmission. This study investigates the role of **BAR (Bin/Amphiphysin/Rvs) domain proteins** as putative regulators of **protein liquid-liquid phase separation (LLPS)**, a mechanism increasingly recognized for organizing cellular components into membraneless organelles. Given their established function in sensing and inducing membrane curvature, BAR domain proteins are strategically positioned to link membrane dynamics with the formation and stability of protein condensates in the complex environment of the central nervous system (CNS) nerve terminal. Our objective was to determine if specific BAR domain proteins interact with and modulate the protein liquid phase, which is hypothesized to concentrate key synaptic components. Using a combination of *in vitro* reconstitution assays, high-resolution live-cell imaging in primary neuronal cultures, and biochemical fractionation of synaptosomes, we demonstrate that select BAR domain proteins, particularly those involved in endocytosis, significantly alter the size and fluidity of protein condensates. Specifically, we found that the concave surface of the BAR domain promotes the recruitment of phase-separating proteins to the membrane interface, suggesting a mechanism for spatially restricting the liquid phase. These findings establish BAR domain proteins as critical molecular links between membrane topology and the spatiotemporal control of protein LLPS, providing novel insights into the regulation of synaptic function and potential dysfunction in neurological disorders.