Ciliary and Osteogenic Defects as Central Drivers of AIS in POC5 Mutation Models.

Adolescent idiopathic scoliosis (AIS) is a multifactorial spinal deformity with poorly understood molecular mechanisms. This study investigates the role of the centrosomal protein POC5 in AIS pathogenesis using in vitro cellular systems and in vivo vertebrate models. POC5 mutations were found to disrupt centrosomal localization, impair ciliogenesis, alter cell-cycle progression, and reduce osteogenic differentiation. Functional analyses in zebrafish and mouse models revealed spinal deformities, retinal abnormalities, and multisystem defects consistent with ciliopathy-related phenotypes. These findings support a model in which POC5-dependent dysfunction contributes to AIS through impaired mechano-transduction and altered skeletal development.