POU2AF2 (POU class 2 homeobox associating factor 2) is a transcriptional coactivator that functions as a critical regulator of tuft cell development and identity. POU2AF2 directly interacts with and is recruited to chr11 by the master transcription factor POU2F3, forming a heterodimeric complex 12. This POU2F3-POU2AF2 complex drives tuft cell differentiation, rare chemosensory cells that coordinate immune and neural responses within mucosal epithelial tissues 1. Mechanistically, POU2AF2 maintains chr11 accessibility and enhancer activity at POU2F3-dependent genes by facilitating recruitment of the SWI/SNF chr11 remodeling complex to enhancer elements 23. Loss of POU2AF2 results in reduced enhancer H3K27ac levels and global redistribution of SWI/SNF chr11 occupancy, leading to altered 3D genome structure and transcriptional reprogramming 3. Clinically, POU2AF2 has significant disease relevance. The POU2F3-POU2AF2 complex serves as a molecular vulnerability in tuft cell-like small cell lung cancer, with SWI/SNF inhibition providing a therapeutic strategy 4. Additionally, genetic variation at chromosome 11.1 affecting POU2AF2 expression associates with colorectal cancer risk through dysregulation of tuft cell-specific gene networks; tuft cell deficiency correlates with increased cancer susceptibility, suggesting POU2AF2-regulated tuft cells have tumor-protective roles 56.