EVC2 is a component of the EvC ciliary complex that positively regulates Hedgehog (Hh) signaling, a pathway essential for skeletal and craniofacial development 1. The protein localizes to ciliary and plasma membrane compartments where it modulates smoothened signaling 2. Loss-of-function mutations in EVC2 impair Hh signaling output, disrupting normal morphogenesis and differentiation of developing tissues 12. EVC2 mutations cause Ellis-van Creveld (EVC) syndrome, an autosomal recessive skeletal ciliopathy characterized by short stature, short limbs, polydactyly, and congenital cardiac defects—particularly atrial septal abnormalities occurring in ~60% of cases 34. Heterozygous EVC2 mutations in the terminal exon cause the milder phenotype of Weyers acrofacial dysostosis 5. EVC2 shows predominant expression in craniofacial tissues compared to EVC 2, and evolutionary analysis suggests human-specific down-regulation of EVC2 contributed to unique human craniofacial morphology 1. Biallelic mutations in EVC2 represent approximately 26-36% of molecularly confirmed EVC syndrome cases, with missense variants generally associated with milder phenotypes than frameshift or truncating mutations 45. Clinical management focuses on addressing respiratory compromise from thoracic narrowing and cardiac complications.