RFXANK (regulatory factor X associated ankyrin containing protein) is a crucial transcriptional regulatory protein that serves as one of three subunits of the heterotrimeric RFX complex essential for MHC class II gene expression 1. The protein functions by assembling with RFXAP and RFX5 to form the RFX complex, which binds to MHC class II promoters and facilitates transcriptional activation in conjunction with CIITA (class II transactivator) 2. RFXANK contains ankyrin repeats that are critical for protein-protein interactions, particularly with RFXAP, as mutations affecting these domains (such as D121V) prevent RFX complex formation 1. The protein also interacts with other transcription factors including RFX7 through recognition of PXLPXL motifs 3. RFXANK mutations cause MHC class II deficiency (bare lymphocyte syndrome type II), a severe combined immunodeficiency characterized by absent MHC class II expression on antigen-presenting cells 4. This results in recurrent severe infections, persistent diarrhea, and pneumonia, with RFXANK mutations being among the most frequent causes of this condition 5. Patients typically require hematopoietic stem cell transplantation as the only curative treatment 6. The protein's essential role in immune surveillance makes it a critical component of adaptive immunity.