HOXB4 is a sequence-specific transcription factor that plays critical roles in hematopoietic stem cell (HSC) self-renewal and differentiation 1. The protein functions as a key regulator of the balance between HSC self-renewal and differentiation, with its expression levels determining therapeutic outcomes - proper dosage promotes beneficial HSC expansion while excessive levels can perturb normal lineage differentiation 2. HOXB4 achieves its effects by binding to specific DNA sequences and regulating downstream target genes, including METTL7B, which it transcriptionally suppresses 3. In disease contexts, HOXB4 frequently functions as a tumor suppressor. In lung adenocarcinoma, HOXB4 expression is reduced due to DNA hypermethylation, and its restoration inhibits cell proliferation, invasion, and migration while promoting apoptosis through regulation of the RAP1 signaling pathway and epithelial-mesenchymal transition 4. Similarly, in hepatocellular carcinoma, HOXB4 suppresses tumor progression and enhances immune infiltration by modulating the METTL7B/TKT axis and reducing PD-L1 expression 3. Clinical applications include ex vivo HSC expansion using TAT-HOXB4 protein for transplantation therapies 5, and HOXB4 can enhance mesenchymal stem cell proliferation without affecting their surface markers 6.