AbstractProtein phase separation has been shown to be a major governing factor in multiple cellular processes, especially ones concerning RNA and RNA-binding proteins. Despite many key observations, the exact structural characteristics of proteins involved in the process are still not fully deciphered. In this work we show that proteins harbouring sequences with specific regions of charged residues are significantly associated with phase separation phenomena. In particular, regions with repetitive arrays of alternating charges (termed charged residue repeats, CRRs) show the strongest association, whereas segments with generally high charge density (charge-dense regions, CDRs) and single alpha-helices (SAHs) show also detectable but weaker connections.It is known to contribute to the formation of membrane-less organelles (MLOs) and to an extent the aggregation of proteins. The causes and consequences of phase separation has been a rigorously researched topic in the last few years, as the condensation of specific phase-separating proteins is known to promote several diseases.In this work we carried out a computational analysis to examine the presence of repetitive segments with high charge density in proteins prone to phase separation. Free resources such as the Charged Single α-Helix (CSAH) web server and the PhaSepDB online database were used to examine possible links between the charged side-chain content of protein sequences and their partition into membrane-less condensates. Furthermore, we carried out the development of a novel algorithm aimed to detect a larger variety of charged protein segments, in order to examine their relationship to the phenomenon. Fisher’s exact test of independence was implemented on several generated data sets to confirm correlation between charged residue repeats (CRRs) and charge-dense regions (CDRs) within human protein sequences and their affinity for phase separation.