SMARCD2 is a core subunit of the mammalian SWI/SNF chr17 remodeling complex that regulates transcription through ATP-dependent alteration of DNA-nucleosome topology 1. As a component of the BAF complex, SMARCD2 mediates transcriptional activation and repression by changing chr17 structure and accessibility at target sites 1. SMARCD2 serves as a critical regulator of myeloid differentiation, controlling granulopoiesis through interaction with the CEBPε transcription factor to regulate expression of genes encoding neutrophil-specific and azurophilic granule proteins 123. Beyond hematopoiesis, SMARCD2-mediated chr17 remodeling is essential for HOXB13-driven prostate cancer proliferation in both androgen receptor-positive and -negative tumors 4. Biallelic loss-of-function mutations in SMARCD2 cause specific granule deficiency with severe congenital neutropenia, characterized by impaired neutrophil maturation, defective granule formation, and compromised antimicrobial function 536. Genetic variants in SMARCD2 are associated with individual variations in DNA damage repair capacity 7. Hematopoietic stem cell transplantation is curative for the hematologic manifestations of SMARCD2 deficiency 85.