DYNC1H1 encodes cytoplasmic dynein 1 heavy chain, a motor protein essential for retrograde intracellular transport of vesicles and organelles along microtubules 1. The protein exhibits ATPase activity and plays critical roles in mitotic spindle assembly and metaphase plate congression through its core complex function in neuronal axons 1. DYNC1H1 is ubiquitously expressed, yet pathogenic variants show selective motor neuron involvement 1. Dominant heterozygous DYNC1H1 mutations cause a broad spectrum of neurodevelopmental and neuromuscular disorders with age-dependent progression 1. Clinical manifestations include infantile epileptic spasms syndrome (50% of epilepsy cases), Lennox-Gastaut syndrome, and drug-resistant epilepsy with malformations of cortical development present in 92% of affected individuals 23. Additional features include developmental delay, sensory neuropathy (onset ~10.6 years), autonomic dysfunction, movement disorders, and novel multisystem involvement including immunodeficiency and sensorineural hearing loss 1. Stalk domain variants associate with more severe phenotypes 2. Recent evidence indicates viral infections (Herpesviridae, Ross River fever, SARS-CoV-2) can trigger neurodegeneration, suggesting dynein's role in antiviral immunity 1. Animal models demonstrate cortical neuronal migration abnormalities and behavioral deficits 4. DYNC1H1 variants represent a significant cause of monogenic intellectual disability, particularly in neurodevelopmental cohorts 5.