“…The physiological concentration of huntingtin in the human brain, estimated to be low nanomolar (Macdonald et al, 2014), is likely too low for liquid-liquid phase separation in the presence of even one binding partner at its physiological concentration (Posey et al, 2018). Notwithstanding limited reports to the contrary (Fisher et al, 2021;Peskett et al, 2018;Wan et al, 2021) --which we respectfully attribute to known effects of flanking domain interactions and partitioning into pre-existing protein compartments (Duennwald et al, 2006a(Duennwald et al, , 2006bJiang et al, 2017) --our findings corroborate prior demonstrations that polyQ does not phase separate prior to amyloid formation, whether expressed in human neuronal cells (Colby et al, 2006;Kakkar et al, 2016), C. elegans body wall muscle cells (Sinnige et al, 2021), or [pin -] yeast cells (Duennwald et al, 2006a(Duennwald et al, , 2006bJiang et al, 2017).…”