HOXC4 is a sequence-specific transcription factor that regulates anterior-posterior pattern specification during development 1. In hematopoiesis, HOXC4 promotes expansion of human hematopoietic stem and progenitor cells, expanding CD34+ cells 3-6 fold ex vivo and improving in vivo engraftment 1. Mechanistically, HOXC4 regulates downstream genes including MEF2C, EZH2, and DBF4 that are critical for stem cell fate and expansion 1, and operates through NF-κB signaling and cell-cycle regulation to promote erythroid-megakaryocyte progenitor production 2. HOXC4 expression is developmentally regulated across lymphoid differentiation stages, present in CD34+/CD38low stem cells through mature lymphocytes 3, and correlates with keratinocyte differentiation in normal skin 4. In disease contexts, HOXC4 has significant clinical relevance: aberrant overexpression is associated with aggressive prostate cancer and predicts recurrence 5, and altered DNA hydroxymethylation of the HOXC4 promoter correlates with reduced sperm concentration in oligoasthenozoospermia 6. Early post-stroke HOXC4 expression is associated with stroke outcomes 7. These findings suggest HOXC4 functions in both normal hematopoietic expansion and aberrant cell proliferation in cancer.