AP1S2 encodes a subunit of the adaptor protein complex 1 (AP1), which functions in protein sorting and vesicle trafficking within the late-Golgi/trans-Golgi network and endosomes 1. The protein plays a crucial role in synaptic vesicle cycling, specifically in vesicle re-uptake processes 1. AP1S2 is also involved in monocyte-to-macrophage maturation through the ATF3-AP1S2 signaling axis, where it regulates macrophage polarization and inflammatory responses in intestinal tissues 2. Pathogenic variants in AP1S2 cause Pettigrew syndrome, an X-linked neurodevelopmental disorder characterized by intellectual disability, delayed walking and speech development, hypotonia, seizures, and dysmorphic features 345. Different mutation types produce varying phenotypes: splice site mutations are more associated with seizures, while nonsense mutations increase susceptibility to microcephaly 3. The gene is located on chromosome X and represents one of the established X-linked genes associated with congenital hydrocephalus 6. Recent genome-wide studies have confirmed AP1S2's association with autism spectrum disorder, highlighting its broader role in neurodevelopmental pathways 7.