There is a sex bias in human health and disease and some of these biases could be explained by the proteins expressed on the X and Y chromosomes. Many of the X chromosome protein functions are well known, but how they compare to the Y chromosome homologs is unknown. We set out to understand a particular XY pair, DDX3X and DDX3Y, which are DEAD-box RNA helicases with intrinsically disordered regions. Through the use of biochemical and single molecule approaches, we teased apart the functional differences of these proteins and how that may link to the sex bias in disease propensity. We find that these proteins have distinct propensities to undergo liquid-liquid phase separation (LLPS) in vitro and in cells. We find that the LLPS is stronger for DDX3Y compared to DDX3X and the stronger ATPase activity of DDX3X drives the discrepancy is LLPS dissolution. Not only do these proteins phase separate differently at the microscopic level, but we find that they form nano-sized RNA-protein clusters (RPCs) both in vitro and in cells that we believe nucleate LLPS. These clusters of protein form under non-stressed conditions and are associated with increased catalytic activity, which indicates that these clusters may be important for efficient catalytic activity of these proteins. Interestingly, DDX3X is found to have higher overall helicase activity. We find that the N terminal intrinsically disordered region (IDR) drives the formation of these clusters, and both the N and C terminal IDRs are important for the catalytic activity. These findings provide a basis for studying other sex biased protein pairs and how they contribute to the sex bias in human health and disease.