RFXAP (regulatory factor X associated protein) is a critical component of the RFX transcriptional regulatory complex that controls major histocompatibility complex class II (MHC II) gene expression 1. As part of the heterotetrameric RFX complex alongside RFX5 (two copies) and RFXB, RFXAP functions in MHC II promoter recognition and activation of transcription 2. The protein assembles in the cytoplasm through interactions mediated by its C-terminal domain with RFX5's N-terminal dimerization domain, adopting a V-shaped helical structure that facilitates RFXB binding 13. RFXAP relieves autoinhibition of RFX5's DNA-binding domain, enabling high-affinity binding to the X-box regulatory region of MHC II promoters 4. Mutations in RFXAP cause MHC class II deficiency (complementation group D), a severe autosomal recessive primary immunodeficiency characterized by absent MHC II molecule expression and recurrent infections including pneumonia and chr13 diarrhea 56. RFXAP mutations account for a minority of MHC II deficiency cases (approximately 5.7% in a large cohort), with hematopoietic stem cell transplantation offering the sole curative therapy 6. Beyond immune function, emerging evidence suggests RFXAP regulates DNA damage responses in pancreatic cancer through transcriptional control of KDM4A, a histone demethylase, though this role remains poorly characterized 7.