DYNC2I1 encodes dynein 2 intermediate chain 1, a non-catalytic accessory component of the cytoplasmic dynein 2 complex that drives retrograde intraflagellar transport (IFT) in cilia and flagella 1. The protein plays a major role in retrograde ciliary protein trafficking and is required to maintain a functional transition zone 2. DYNC2I1 localizes to ciliary structures and functions as part of the dynein-2 motor complex that transports cargo along microtubules within cilia in concert with the IFT system. Mechanistically, pathogenic variants of DYNC2I1 demonstrate compromised ability to interact with other dynein-2 subunits like DYNC2H1 and WDR60, leading to ciliary defects 3. Disease relevance includes associations with short-rib thoracic dysplasia, a lethal skeletal ciliopathy characterized by shortened ribs, polydactyly, and extraskeletal phenotypes. Compound heterozygous mutations combining deletion and missense variants cause more severe ciliary dysfunction than individual variants alone 3. Clinical significance extends beyond skeletal ciliopathies, as bi-allelic DYNC2I1 variants (one germline, one somatic) have been identified in hypothalamic hamartomas, reconceptualizing this disorder as a ciliopathy 4. The gene also shows population-specific variation in repeat composition that may contribute to genomic diversity 5.