Complex coacervation is an emerging liquid/liquid phase separation (LLPS) 
phenomenon that behaves as a membrane-less organelle in living cells. Yet while 
one of the critical factors for complex coacervation is temperature, little 
analysis and research has been devoted to the temperature effect on complex 
coacervation. Here, we performed a complex coacervation of cationic protamine 
and multivalent anions (citrate and tripolyphosphate (TPP)). Both mixtures 
(i.e., protamine/citrate and protamine/TPP) underwent coacervation in an aqueous 
solution, while a mixture of protamine and sodium chloride did not. 
Interestingly, the complex coacervation of protamine and multivalent anions 
showed upper critical solution temperature (UCST) behavior, and the coacervation 
of protamine and multivalent anions was reversible with solution temperature 
changes. The large asymmetry in molecular weight between positively charged 
protamine (~4 kDa) and the multivalent anions (<0.4 kDa) and strong 
electrostatic interactions between positively charged guanidine residues in 
protamine and multivalent anions were likely to contribute to UCST behavior in 
this coacervation system.