IFT56 (also known as TTC26) is a core component of the intraflagellar transport (IFT)-B complex essential for ciliary protein trafficking 1. As part of the IFT-B core subcomplex, IFT56 mediates anterograde transport of specific ciliary cargo proteins required for motility and couples GLI2/GLI3 accumulation at ciliary tips with their dissociation from SUFU, thereby regulating Hedgehog signaling 2. IFT56 maintains IFT-B complex integrity and proper ciliary localization of IFT-B components through direct interactions with IFT46 and other binding partners, including KIF17 3. Loss-of-function mutations in IFT56 cause ciliopathies characterized by multiple congenital anomalies affecting biliary, renal, neurologic, and skeletal systems. Disease severity exhibits striking genetic background-dependent variation; Ift56 homozygous mutants are viable with male sterility in BALB/cByJ mice but perinatal lethal with skeletal defects and tracheoesophageal fistulas in C57BL/6J mice, suggesting modifier loci influence ciliopathy phenotypes 4. These findings demonstrate IFT56's critical role in maintaining ciliary structure and function while highlighting genetic complexity in ciliopathy pathogenesis relevant for human diagnostics.