AP-1 complex subunit sigma-2

AP-1 complex subunit sigma-2 (AP1S2) is a component of the clathrin-associated adaptor protein complex 1, which mediates protein sorting in the late-Golgi/trans-Golgi network and endosomes by recruiting clathrin to membranes and recognizing cargo sorting signals (UniProt: P56377). The protein functions in intracellular trafficking and membrane protein organization across multiple cellular compartments.

AP1S2 is associated with Pettigrew syndrome, an X-linked disorder characterized by intellectual disability, choreoathetosis, hydrocephalus, and seizures (UniProt: P56377). This link highlights the protein's importance in neurological function, particularly in developmental contexts.

AP1S2 is upregulated in Alzheimer's disease brain tissue. Human post-mortem AD brain compared to age-matched controls showed elevated AP1S2 levels across measured subcellular fractions, with a mean log2 fold-change of 1.03 (Chaparral AD proteomics). This upregulation suggests potential involvement in AD-related pathological processes, though the specific mechanistic contribution to neurodegeneration remains to be elucidated.