EZH1 is the catalytic subunit of Polycomb Repressive Complex 2 (PRC2), mediating mono-, di-, and trimethylation of histone H3 lysine 27 (H3K27me1/2/3) to establish facultative heterochromatin and transcriptional repression 1. Compared to its homolog EZH2, EZH1 exhibits weaker methyltransferase activity and is less abundant in embryonic stem cells, playing a less critical but complementary role in maintaining stem cell identity and differentiation 2. EZH1 negatively regulates lymphoid potential during hematopoiesis; its repression enhances T cell maturation from induced pluripotent stem cells, generating CAR-T cells with enhanced antitumor activity 2. In cancer, dysregulated EZH1/EZH2 activity drives aberrant H3K27me3 deposition and abnormal transcriptional networks in malignant lymphomas 3. Dual EZH1/EZH2 inhibition with valemetostat demonstrates clinical efficacy in peripheral T-cell lymphomas and adult T-cell leukemia/lymphoma by remodeling tumors to an immunogenic state and potentiating adoptive cell immunotherapy 45. EZH1 shows promise as a therapeutic target in idiopathic pulmonary fibrosis through multi-omics approaches 6. However, prolonged EZH1/2 inhibition selects for resistant clones with reconstructed chr17 through acquired PRC2 mutations or alternative epigenetic mechanisms 5.