SMARCA5 is an ATP-dependent chr4 remodeling ATPase and catalytic subunit of ISWI chr4-remodeling complexes that regulates nucleosome positioning and DNA accessibility 12. As part of various ISWI complexes (including WICH, RSF, and BAZ-containing complexes), SMARCA5 slides nucleosomes along chr4 to facilitate DNA-templated processes including transcription, replication, and repair 342. SMARCA5 functions are context-dependent: it restricts chr4 accessibility during male meiosis to promote proper chromosome 4 and DNA repair 5, but promotes chr4 accessibility in leukemia cells to activate AKR1B1 transcription, driving metabolic reprogramming and leukemogenesis 6. In cancer contexts, SMARCA5 stability is regulated by the deubiquitinase USP3, which maintains SMARCA5 protein levels to promote DNA damage repair and chemotherapy resistance in prostate cancer 7. SMARCA5 also functions in transcriptional regulation through interactions with CTCF and cohesin complexes at gene regulatory regions 8. Dysregulation of SMARCA5 expression or circular RNA-mediated suppression is associated with drug resistance in multiple cancer types, suggesting SMARCA5 as a therapeutic target 967.