Adaptor-related protein complex 4 subunit beta-1 (AP4B1)

Adaptor-related protein complex 4 subunit beta-1 (AP4B1) is a critical component of the heterotetrameric AP-4 complex, which facilitates the selective sorting and transport of cargo proteins from the trans-Golgi network to the endosomal-lysosomal system [1, 10]. In neurons, AP4B1 is essential for the proper localization of cargo proteins like ATG9A, which is critical for autophagy and the maintenance of axonal integrity [1, 18]. Biallelic loss-of-function mutations in the AP4B1 gene lead to a deficiency of the AP-4 complex, resulting in Hereditary Spastic Paraplegia Type 47 (SPG47), a rare neurodevelopmental disorder characterized by progressive spasticity, intellectual disability, and epilepsy [1, 3]. Therapeutic development for SPG47 primarily focuses on gene replacement therapy, such as BFB-101 (AAV9/AP4B1), which aims to restore functional protein levels within the central nervous system [3, 8]. These therapies utilize viral vectors to deliver a healthy copy of the AP4B1 gene, typically via intra-cisterna magna injection to achieve broad distribution across the brain and spinal cord [3, 6]. Clinical and preclinical monitoring involves the use of biomarkers such as plasma neurofilament light (NfL) to assess neurodegeneration, while safety assessments focus on potential immunogenicity and the risks associated with the delivery procedure [1, 2, 17].

Other names

AP-4 complex subunit beta-1BETA-4Adaptor related protein complex 4 beta 1 subunitSPG47CPSQ5Beta4-adaptin

Gene replacement therapy