HOXD13 is a sequence-specific transcription factor that plays critical roles in developmental regulation and disease pathogenesis. As a developmental regulator, HOXD13 functions in limb development, with pathogenic variants causing synpolydactyly type 1 (SPD1), characterized by webbed fingers and extra digits 1. The most common pathogenic variants are alanine repeat expansions, which correlate with phenotype severity 1. Mechanistically, disease-associated repeat expansions alter HOXD13's phase separation capacity and its ability to co-condense with transcriptional co-activators, leading to perturbation of transcriptional condensate composition and altered gene expression programs 2. Beyond developmental disorders, HOXD13 has emerged as a significant factor in cancer progression. In colorectal cancer, HOXD13 is upregulated and promotes immunosuppression by transcriptionally upregulating AREG and PILRA, leading to M2-type macrophage polarization and CD8+ T cell suppression 3. In gliomas, HOXD13 functions as a master regulator of IDH-mutant astrocytoma evolution, with treatment-associated epigenomic changes leading to HOXD13 activation 4. HOXD13 also plays a role in myelodysplastic syndromes, where NUP98-HOXD13 fusion proteins contribute to disease pathogenesis through effects on bone marrow mesenchymal stromal cells 5.