AP-3 complex subunit beta-2

AP3B2 encodes AP-3 complex subunit beta-2, a core component of the adaptor protein complex 3 (AP-3) that functions in protein sorting within the trans-Golgi network and endosomes (UniProt: Q13367). The AP-3 complex mediates recognition of cargo sorting signals and, in conjunction with the BLOC-1 complex, is required for targeting proteins into vesicles at neuronal cell bodies for delivery to neurites and nerve terminals, implicating it in synaptic function.

AP3B2 is associated with developmental and epileptic encephalopathy 48 (DEE48; MIM 617276), an autosomal recessive early-onset epilepsy characterized by seizures, global developmental delay, intellectual disability, and severe neurodevelopmental impairment (UniProt: Q13367). The protein's role in neuronal vesicle transport and lysosomal-related organelle biogenesis underscores its importance in neuronal homeostasis.

In Alzheimer's disease, AP3B2 is downregulated in post-mortem human brain tissue compared to age-matched controls (mean log2FC −1.64) as measured by TMT-labeled proteomics across subcellular fractions (Chaparral AD proteomics). This reduction in AP-3 subunit levels may impair vesicular trafficking and lysosomal protein sorting, processes implicated in amyloid-β and tau accumulation and clearance in AD pathogenesis.