The study investigates the phase separation of signaling molecules in T cell receptor (TCR) signal transduction. By biochemically reconstituting a 12-component signaling pathway on model membranes, the researchers found that TCR phosphorylation triggers the spontaneous formation of liquid-like clusters of downstream signaling proteins. These clusters, enriched in kinases and excluded phosphatases, enhance actin filament assembly by recruiting and organizing actin regulators. The results demonstrate that protein phase separation creates a distinct physical and biochemical compartment that facilitates signaling, providing insights into how clustering promotes biochemical reactions and signaling responses.The study investigates the phase separation of signaling molecules in T cell receptor (TCR) signal transduction. By biochemically reconstituting a 12-component signaling pathway on model membranes, the researchers found that TCR phosphorylation triggers the spontaneous formation of liquid-like clusters of downstream signaling proteins. These clusters, enriched in kinases and excluded phosphatases, enhance actin filament assembly by recruiting and organizing actin regulators. The results demonstrate that protein phase separation creates a distinct physical and biochemical compartment that facilitates signaling, providing insights into how clustering promotes biochemical reactions and signaling responses.