Liquid-liquid phase separation of intrinsically disordered proteins (IDPs) is a major undergirding factor in the regulated formation of membraneless organelles in the cell. The phase behavior of an IDP is sensitive to its amino acid sequence. Here we apply a recent random-phase-approximation polymer theory to investigate how the tendency for multiple chains of a protein to phase-separate, as characterized by the critical temperature T* cr , is related to the protein's single-chain average radius of gyration hR g i. For a set of sequences containing different permutations of an equal number of positively and negatively charged residues, we found a striking correlation T* cr $ hR g i Ăg with g as large as $6.0, indicating that electrostatic effects have similarly significant impact on promoting single-chain conformational compactness and phase separation. Moreover, T* cr f ĂSCD, where SCD is a recently proposed ''sequence charge decoration'' parameter determined solely by sequence information. Ramifications of our findings for deciphering the sequence dependence of IDP phase separation are discussed.The biological functions and disease-causing malfunctions of proteins are underpinned by their structures, dynamics, and myriad intra-and intermolecular interactions. Many critical cellular functions are carried out by intrinsically disordered proteins or protein regions (collectively abbreviated as ''IDPs'' here) with sequences that are less hydrophobic than those of globular proteins, but are enriched in charged, polar, and aromatic residues (1-6). At least 75% of IDPs are polyampholytes (7,8) in that they contain both positively and negatively charged residues (9,10). Accordingly, electrostatic effects are important in determining individual IDPs' conformational dimensions (8,11,12) and binding (13,14). Charge-charge interactions are often significant in the recently discovered phenomenon of functional IDP liquid-liquid phase separation as well (15)(16)(17)(18)(19)(20)(21)(22). IDP phase separation appears to be the physical basis of membraneless organelles, performing many vital tasks. Recent examples include subcompartmentalization within the nucleolus (22) and synaptic plasticity (21). Malfunction of phase separation processes can lead to disease-causing amyloidogenesis (18) and neurological disorders (21). Speculatively, membraneless liquid-liquid phase separation of biomolecules might even have played a role in the origins of life (23).Electrostatic effects encoded by a sequence of charges depend not only on the total positive and negative charges or net charge (24,25) but also the charge pattern (8). For IDPs, this was demonstrated by Das and Pappu (8), who conducted explicit-chain, implicit-solvent conformational sampling of 30 different sequences, each composed of 25 lysine (K) and 25 glutamic acid (E) residues (termed ''KE sequences'' hereafter). They found that the average radius of gyration, hR g i, is strongly sequence dependent, and is correlated with a charge pattern parameter k that quantifie...