AP-4 complex subunit epsilon-1 (AP4E1)

AP-4 complex subunit epsilon-1 (AP4E1) is a critical component of the heterotetrameric adaptor protein complex 4 (AP-4), which mediates the sorting and transport of transmembrane cargo from the trans-Golgi network to the endosomal-lysosomal system (UniProt, PubMed: 10066790). It plays a vital role in neuronal homeostasis by ensuring the proper localization of proteins such as ATG9A, which is essential for autophagosome biogenesis and autophagic flux (Ma'ayan Lab, PubMed: 26542808). Loss-of-function mutations in the AP4E1 gene are the primary cause of Hereditary Spastic Paraplegia type 51 (SPG51), a neurodevelopmental disorder characterized by progressive spasticity, intellectual disability, and microcephaly (GeneCards, OMIM: 607244). Additionally, heterozygous variants in AP4E1 have been associated with familial persistent stuttering (PubMed: 26542808). While there are currently no approved small-molecule drugs targeting AP4E1, it is a significant focus for gene replacement therapies aimed at restoring AP-4 complex function in affected patients (Open Targets). Research also suggests a potential link between AP-4 deficiency and broader neurodegenerative processes, including Alzheimer's disease (Ma'ayan Lab).

Other names

Adaptor related protein complex 4 subunit epsilon 1AP-4 adaptor complex subunit epsilonAdaptor-related protein complex 4 subunit epsilon-1Epsilon subunit of AP-4Epsilon-adaptinSPG51CPSQ4STUT1

None currently approved; gene replacement therapy is under investigation to restore protein function and AP-4 complex assembly in deficiency syndromes.