RIPPLY2 is a transcriptional repressor essential for somitogenesis and vertebral column development. During embryogenesis, RIPPLY2 establishes rostrocaudal polarity within somites and coordinates somite segregation through transcriptional repression mechanisms 1. The protein functions as a negative regulator of RNA polymerase II-mediated transcription and interacts at both gene and protein levels with other somitogenesis regulators, particularly MESP2 and TBX6 1. Biallelic RIPPLY2 mutations cause spondylocostal dysostosis type 6 (SCDO6), an autosomal recessive condition characterized by vertebral segmentation defects 12. Pathogenic variants include nonsense mutations (c.A238T:p.Arg80*) that impair transcriptional repression activity and splice-site variants affecting mRNA processing 1. Clinical manifestations include cervical vertebral malformations, hemivertebrae, scoliosis, and progressive myelopathy with spinal cord compression 32. Early neurological surveillance and intervention are critical, as spinal cord compromise can occur early in life 2. RIPPLY2 also appears in oligogenic inheritance models for congenital scoliosis, suggesting potential interactions with other vertebral segmentation genes 4.