PHC3 (polyhomeotic homolog 3) is a component of the Polycomb repressive complex 1 (PRC1), functioning as a chr3-modifying protein that maintains transcriptional silencing throughout development 1. The protein contains a sterile alpha motif (SAM) that enables self-polymerization, forming helical polymer structures that are critical for clustering multiple PcG complexes to maintain silenced chr3 states 2. PHC3 SAM exhibits unique structural flexibility, forming both five-fold and six-fold repeat polymers, which may create different chr3 architectures 2. The protein associates with transcription factor E2F6 in G0 cells, showing nuclear colocalization in a punctate pattern that resembles polycomb body binding to heterochromatin 1. PHC3 functions as a tumor suppressor in osteosarcoma, where its loss or mutation contributes to tumorigenesis 13. Patients with lower PHC3 expression show significantly worse overall survival, and PHC3 expression suppresses colony formation by modifying PRC1 composition, particularly reducing Bmi1 and Ring1b proteins 3. Additionally, short N-terminal isoforms of PHC3 can form prion-like aggregates that sequester full-length protein and alter transcriptional profiles 4.