GSE1 (genetic suppressor element 1) is a proline-rich coiled-coil protein that functions as a multifaceted oncogenic regulator across multiple cancer types. Primary Function: GSE1 serves as a chr16-associated protein that interacts with the HDAC1/CoREST co-repressor complex 1 and links this complex to DNA damage responses through coordination of deacetylase, demethylase, and deubiquitinase activities 2. Mechanism: GSE1 promotes cancer progression by suppressing tumor suppressor genes (KLF6 in lung cancer 1, TACSTD2 in prostate cancer 3) and activating oncogenic pathways (SLC7A5 in gastric cancer 4, BCL-2 in gastric cancer 5). GSE1 is regulated post-transcriptionally by multiple microRNAs including miR-200b/c, miR-489-5p, and miR-144-3p 467. Disease Relevance: GSE1 overexpression correlates with poor survival outcomes and metastasis in gastric 4, breast 6, lung 1, and prostate cancers 3, and promotes trastuzumab resistance in HER2-positive gastric cancer 5. Clinical Significance: GSE1 represents a promising therapeutic target, with LSD1 inhibitors triggering myeloid differentiation in AML through GSE1 downregulation 8, and GSE1 targeting enhancing sensitivity to androgen receptor inhibitors in castration-resistant prostate cancer 3.