EBF4 is a transcription factor that binds to the canonical DNA sequence motif 5'-CCCNNG[GA]G-3' in regulatory regions of immunoregulatory genes 1. It positively modulates transcription of genes including NKG7, GZMA, TBX21, granzyme, and perforin 1. EBF4 plays a critical role in regulating FAS/CD95-mediated apoptosis in cytotoxic NK cells and CD8+ T cells, likely through interaction with STAT3, STAT5, and MAP kinase 3 downstream of interleukin-2 signaling 1. Loss of EBF4 impairs caspase-8 cleavage by increasing c-FLIP stability in the Fas signaling complex 1. EBF4 demonstrates basal expression in human (but not mouse) NK cells and CD8+ T cells, disappearing after activation 1. Clinically, EBF4 methylation patterns are altered in several disease contexts: differential methylation at EBF4 CpG sites was associated with cardiovascular outcomes in very low birthweight adults 23, identified in perinatally-acquired HIV-infected children on antiretroviral therapy 4, and linked to body fat variation 5. EBF4 has also been identified as part of a 5-gene prognostic signature for colon adenocarcinoma 6.