Adaptor related protein complex 4 subunit epsilon 1 (AP4E1) (AP4E1)

Adaptor related protein complex 4 subunit epsilon 1 (AP4E1) is a critical component of the heterotetrameric AP-4 complex, which facilitates the sorting and transport of cargo proteins from the trans-Golgi network to endosomes (UniProt: Q9UPM8). It plays a vital role in maintaining neuronal homeostasis by regulating the trafficking of specific proteins, such as ATG9A, which is essential for autophagy and axonal maintenance (PubMed: 28871040). Mutations in the AP4E1 gene are a known cause of Hereditary Spastic Paraplegia type 50 (SPG50), a rare neurodegenerative disorder characterized by progressive lower limb spasticity and intellectual disability (OMIM: 607244). While not a traditional small-molecule target, AP4E1 is the primary focus of gene therapy efforts aimed at restoring functional protein levels in affected patients. Current clinical research involves the use of AAV9 viral vectors to deliver healthy copies of the gene to the central nervous system to halt disease progression (ClinicalTrials.gov: NCT05286313).

Other names

AP-4 complex subunit epsilon-1Epsilon-adaptin 4AP4ESPG50CPSQ3

Gene replacement therapy via adeno-associated virus (AAV9) vector to restore functional AP-4 complex assembly and intracellular cargo trafficking (PubMed: 33513348).