DLX5 is a transcription factor essential for skeletal development and neuronal differentiation. As a BMP-responsive homeobox protein, DLX5 acts as an immediate early transcriptional activator critical for osteoblast differentiation 1. It directly regulates key osteogenic genes by binding homeodomain-response elements in the ALPL and SP7 promoters in a manner that complements RUNX2 function 2, and stimulates MYC promoter activity to promote osteoblast proliferation 3. During endochondral ossification, DLX5+ perichondrial cells contribute to cortical bone and bone marrow stromal compartments under Hedgehog signaling regulation, with fetal DLX5+ cells becoming an adipogenic stromal subset postnatally 4. Beyond skeletal development, DLX5 functions in nervous system development and germ cell specification. In the basal ganglia, DLX5 works with MEIS2 to direct GABAergic neuron fate by activating projection-neuron-specific enhancers 5. DLX5 expression also enhances specification of human primordial germ cell-like cells from induced pluripotent stem cells 6. Disease associations include autosomal recessive split-hand/foot malformation with sensorineural hearing loss. Additionally, DLX5 is implicated in autism spectrum disorders and may interact with MeCP2 protein pathways relevant to Rett syndrome 7.