NFYA (nuclear transcription factor Y subunit alpha) is a key component of the heterotrimeric NF-Y transcription factor complex that specifically binds to CCAAT box motifs in gene promoters 1. NFYA functions as both a transcriptional activator and repressor depending on cofactor interactions, regulating diverse cellular processes including cell cycle progression, metabolism, and stem cell maintenance. The protein exists in two main splice variants: NFYA-L (long) and NFYA-S (short), which differ in exon 3 inclusion and have distinct functional roles 2. Mechanistically, NFYA binding to target promoters can be regulated by DNA methylation status, with decreased methylation enhancing NFYA binding and subsequent gene transcription 3. NFYA expression is itself regulated by various signaling pathways, including reactive oxygen species-mediated miR-193b targeting under metabolic stress conditions 4. Disease relevance includes roles in cancer progression, where NFYA promotes cell proliferation and metabolic reprogramming 1, and in cardiovascular disease, where NFYA downregulation contributes to pulmonary hypertension through reduced soluble guanylate cyclase expression 4. In acute myeloid leukemia, NFYA splice variant ratios serve as prognostic biomarkers, with NFYA-S predominance associated with better chemotherapy outcomes 2. NFYA also maintains hematopoietic stem cell functionality through kinase-independent interactions 5.