RFX3 is a transcription factor essential for ciliogenesis and pancreatic endocrine development. As a master regulator, RFX3 controls ciliary gene expression by binding X-box motifs in target gene promoters and forming heterodimers with other RFX proteins 1. RFX3 regulates genes required for ciliary assembly (FOXJ1, BBS4) and motility (axonemal dyneins DNAH5, DNAH9, DNAH11), governing both growth and beating efficiency of motile cilia 2. RFX3 activity is post-translationally regulated through auto-fatty acylation at conserved cysteines, which modulates its dimerization and transcriptional capacity 3. In pancreatic development, RFX3 is highly expressed in endocrine progenitors and mature islet cells, where it regulates insulin-secreting beta cell differentiation and suppresses enterochromaffin cell specification 4. Loss of RFX3 impairs beta cell function and reduces hormone-secreting cells. Clinically, RFX3 disruption associates with neurodevelopmental disorders: heterozygous variants cause autism spectrum disorder, intellectual disability, and ADHD through dysregulation of synaptic gene expression and impaired neuronal activity-dependent transcription 56. RFX3 also contributes to congenital heart disease risk through ciliary dysfunction 7. In glioma, elevated circRFX3 stabilizes RFX3 mRNA via HNRNPK recruitment, promoting tumor progression 8. RFX3 is identified as a critical gene in chromosome 9 deletion syndrome 9.