AP-1 complex subunit sigma-1A

AP1S1 encodes AP-1 complex subunit sigma-1A, a 158-amino-acid protein that functions as a component of the clathrin-associated adaptor protein complex 1. This complex mediates protein sorting in the late-Golgi and trans-Golgi network (TGN) by recruiting clathrin to membranes and recognizing sorting signals within transmembrane cargo molecules (UniProt: P61966).

The protein operates in vesicular trafficking pathways critical for protein delivery and compartmentalization. Mutations in AP1S1 are associated with MEDNIK syndrome, a severe neurodevelopmental and systemic disorder marked by psychomotor retardation, peripheral neuropathy, and sensorineural hearing loss (UniProt: P61966).

AP1S1 is downregulated in Alzheimer's disease brain tissue. Post-mortem AD brain samples showed reduced AP1S1 levels compared to age-matched controls (mean log2 fold-change: −1.62), derived from quantitative proteomics across subcellular fractions (Chaparral AD proteomics). This downregulation may reflect compromised vesicular trafficking and protein sorting dysfunction in AD pathology.