Background: Episodic ataxia (EA), characterized by recurrent attacks of cerebellar
dysfunction, is the manifestation of a group of rare autosomal dominant inherited disorders …

Importance Cerebral palsy is a common neurodevelopmental disorder affecting movement
and posture that often co-occurs with other neurodevelopmental disorders. Individual cases …

There are more than 10,000 individual rare diseases and most are without therapy.
Personalized genetic therapy represents one promising approach for their treatment. We …

Background Hereditary spastic paraplegia (HSP) encompasses several rare genetic
disorders characterized by progressive lower extremity spasticity and weakness caused by …

Spastic paraplegia 50 (SPG50) is an ultrarare childhood-onset neurological disorder caused
by biallelic loss-of-function variants in the AP4M1 gene. SPG50 is characterized by …

The adaptor protein complex AP-4 mediates anterograde axonal transport and is essential
for axon health. AP-4-deficient patients suffer from a severe neurodevelopmental and …

BLOC-one-related complex (BORC) is a multiprotein complex composed of eight subunits
named BORCS1–8. BORC associates with the cytosolic face of lysosomes, where it …

Unbiased phenotypic screens in patient-relevant disease models offer the potential to detect
therapeutic targets for rare diseases. In this study, we developed a high-throughput …

Background Adaptor protein complex 4‐associated hereditary spastic paraplegia (AP‐4‐
HSP) is caused by pathogenic biallelic variants in AP4B1, AP4M1, AP4E1, and AP4S1 …

Mutations in any one of the four subunits (ɛ4, β4, μ4 and σ4) comprising the adaptor protein
Complex 4 results in a complex form of hereditary spastic paraplegia, often termed adaptor …