VAX1 is a homeodomain transcription factor that functions as a sequence-specific DNA-binding regulator of gene expression 1. Developmentally, VAX1 is required for dorsoventral specification of the forebrain, axon guidance, and major tract formation [UniProt]. VAX1 plays critical roles in suprachiasmatic nucleus (SCN) development and function, including regulation of vasoactive intestinal peptide expression and circadian output 1. The gene is also essential for gonadotropin-releasing hormone (GnRH) neuron development; heterozygous VAX1 deletion causes subfertility through hypothalamic dysfunction, with reduced GnRH neuron numbers and altered kisspeptin expression 2. VAX1 contributes to neuroretinal and optic development, with homozygous mutations causing microphthalmia, small optic nerves, and corpus callosum agenesis 3. Clinically, VAX1 variants are strongly associated with nonsyndromic cleft lip with or without palate (NSCL/P) across multiple populations 456. Common variants (rs7078160, rs4752028) show significant over-transmission in affected families, with both maternal and paternal contributions 46. Multiple rare missense mutations in VAX1 have been identified in NSCL/P patients, though penetrance appears incomplete 76. VAX1 mutations are also associated with syndromic microphthalmia 3. The gene represents an important susceptibility locus for craniofacial development and reproductive function.