DYNC2LI1 encodes the dynein cytoplasmic 2 light intermediate chain 1, a critical component of the dynein-2 motor complex essential for intraflagellar transport (IFT) within primary cilia 1. The protein is required for dynein-2 complex stability and facilitates retrograde transport of IFT machinery from ciliary tips back to the cell body 12. DYNC2LI1 interacts directly with DYNC2H1 and WDR60 subunits to maintain proper dynein-2 function 2. Loss of DYNC2LI1 function results in variable ciliary length, including hyperelongated cilia, accumulation of IFT-B complex proteins at ciliary tips, and impaired Hedgehog pathway signaling 13. The protein plays a crucial role in regulating ciliary protein trafficking, including Hedgehog pathway receptors Smoothened and GPR161 3. Biallelic mutations in DYNC2LI1 cause skeletal ciliopathies, primarily short-rib thoracic dysplasia 15 with polydactyly (SRTD15), but also contribute to Ellis-van Creveld syndrome 14. Disease-causing variants impair osteogenic differentiation of mesenchymal stem cells through defective Hedgehog signaling and altered GLI3 processing 3. The severity of skeletal ciliopathy phenotypes depends on the combination and functional impact of specific DYNC2LI1 variants 2.