IFT80 is a core component of the intraflagellar transport (IFT) complex B, essential for cilia assembly and maintenance across ciliated organisms 1. Structurally, IFT80 forms a homodimer through its C-terminal α-helical extension, with its N-terminal β-propellers mediating integration into the larger IFT-B complex 2. This homodimerization is absolutely required for ciliogenesis, as demonstrated in CRISPR-engineered mouse cells 2. IFT80 regulates critical developmental processes beyond ciliogenesis. In chondrocyte differentiation, IFT80 modulates Hedgehog signaling through Gli2 while suppressing Wnt signaling to promote chondrogenesis 3. Similarly, in osteogenesis, IFT80 activates Hedgehog/Gli2 pathways and coordinates canonical versus non-canonical Hh signaling to enable osteoblast differentiation [PMID:22771375; 42]. In dental pulp stem cells, IFT80 couples FGF/FGFR1 signaling with Hh/BMP2 pathways to regulate odontogenic differentiation 5. IFT80 mutations cause short-rib thoracic dysplasia and Jeune asphyxiating thoracic dystrophy (JATD), autosomal recessive chondrodysplasias with skeletal abnormalities [PMID:23333501; 65]. Disease-causing missense mutations fail to establish functional IFT particles, while C-terminal deletions abolish dimerization and ciliogenesis rescue 2. Aberrant IFT80 expression promotes gastric and endometrial cancer progression through distinct pathways [PMID:30453504; 75], indicating context-dependent oncogenic roles.