HOXC5 is a sequence-specific transcription factor that functions as a developmental regulator providing cells with positional identity along the anterior-posterior axis 1. Beyond its classical embryonic role, HOXC5 regulates spermatogonial stem cell fate through the WNT/β-catenin signaling pathway, where it promotes proliferation and suppresses apoptosis when activated by the deubiquitinase USP11 2. HOXC5 also functions as a tumor suppressor by repressing telomerase (hTERT) expression during cellular differentiation through both transcriptional mechanisms and via the miR-615-3p microRNA encoded within its intron, creating a feed-forward repression loop that coordinates differentiation 3. Pathologically, HOXC5 exhibits aberrant expression in multiple malignancies. It is aberrantly activated in cervical cancer cells and non-Hodgkin's lymphomas, particularly anaplastic large-cell lymphomas and mucosa-associated lymphomas, where it is absent in normal lymphoid tissues 4 5 6 7. In myeloid leukemias, HOXC5 shows restricted expression in early differentiation stages, suggesting lineage-specific roles 8. During normal skin development, HOXC5 marks early fetal fibroblasts (7-8 weeks) that transition toward papillary and follicular lineages 1. These findings suggest HOXC5 deregulation contributes to malignant transformation and male infertility through disrupted developmental signaling pathways.