Chromatin contains not only heterochromatin (HC) and euchromatins (EC) but also facultative heterochromatin (fHC), which experience the dynamic remodeling between HCs and ECs by different regulators. The regulation of fHCs involves lots of different cell functions, like genomic stability and gene transcription. Heterochromatin protein 1 (HP1) recognizes methylated H3K9 and reshapes the chromatin into the fHCs through liquid-liquid phase separation (LLPS). Among the three members of the HP1 family, HP1α can condensate by itself and HP1β forms granules with the help of TRIM28, while the HP1γ cannot phase separation alone either and the coordinator is still unclear. So, in this study, we investigated the molecular mechanism of how HP1γ interacts with TRIM66 through PxVxL motif. Based on that, we examined the key regions that controlled the TRIM66-HP1γ co-phase separation behaviors both