Concerning the thermodynamic driving forces, basic considerations suggest that PS should in principle be unfavorable because of the entropy penalty of demixing and the formation of an interface, which is associated with a surface energy. However, the surface tensions of biocondensates are typically ultralow (in the range 0.0001 to 0.1 mN/m ; for comparison, the value for the air/water interface is 72 mN/m at 298 K) and the surface energies are thus small. Nevertheless, for PS to occur, these contributions have to be overcome by favorable (preferential) interactions. A simple theoretical approach to understand and analyze this interplay of interaction energy and entropy has been described by Flory and Huggins, who developed a mean-field theory to describe density transitions in polymer solutions and determine whether a given composition exists as a single phase or forms multiple phases at a certain temperature. As a mean-field theory, this approach does not provide insights at the molecular level. It has been highlighted that multivalency is required for PS, which means that the average number of intermolecular connections (per unit volume) that the molecules can establish are important for the formation of a three-dimensional connected meshwork that spans the dense phase . In this context, the stickers-and-spacers model is a powerful conceptual framework to rationalize and predict the sequence-dependence of the PS tendency. According to this model, the individual amino acids in the polypeptides are categorized as either stickers or spacers. PS is driven by attractive interactions between stick-ers, such as electrostatic attraction, H-bonding, hydrophobic (non-polar) or van der Waals contacts, cation-π, π-π, or sp 2 -π interactions, etc . Spacers connect the stickers and are largely non-interacting. Especially aromatic residues have been identified as stickers. Furthermore, particularly arginine (but not so much lysine) fosters PS through interactions with aromatic groups. Beyond their abundance in the polypeptide chain, the patterning of the stickers along the linear sequence also plays a key role in the topology and mesh size of the network, and descriptors such as sequence charge decoration and sequence hydropathy decoration have been introduced. In addition to such single residuebased descriptors, it has also been highlighted that IDRs can contain interaction motifs, such as low-complexity aromatic-rich kinked segments or reversible amyloid cores, which involve transient structuring of the polypeptide backbone and the formation of cross-β motifs .