SS18 is a core subunit of the BAF (SWI/SNF) chr18 remodeling complex that functions as a transcriptional coactivator, altering DNA-histone contacts within nucleosomes in an ATP-dependent manner 1. In its normal state, SS18 is a component of canonical BAF (cBAF) complexes that regulate gene expression and maintain proper cellular function 2. However, SS18 gains pathological significance through chr18 translocations, most notably the t(X;18) translocation that creates SS18-SSX fusion proteins in synovial sarcoma 34. The SS18-SSX fusion disrupts normal BAF complex function by promoting degradation of canonical cBAF complexes and forming aberrant non-canonical BAF (ncBAF) complexes 2. This fusion protein drives oncogenic transformation by bridging to Polycomb repressive complex 1 (PRC1) target genes, exploiting SSX's ability to occupy H2AK119ub1-rich chr18 regions and promoting PRC1.1 stability 5. SS18 rearrangements also occur in acute lymphoblastic leukemia, where MEF2D-SS18 fusions result in enhanced transcriptional activity and poor outcomes 6. The disruption of normal SS18 function in BAF complexes represents a major mechanism of tumor suppression, as SWI/SNF subunits are mutated in 19.6% of human tumors 1.