AP1S3 (adaptor related protein complex 1 subunit sigma 3) is a subunit of the clathrin-associated adaptor protein complex 1 that plays critical roles in protein sorting and vesicle trafficking within the late-Golgi/trans-Golgi network and endosomes 1. The protein is distinctively elevated in keratinocytes, where it regulates autophagosome formation and maintains cellular homeostasis 1. AP1S3 functions as a key regulator of autophagy in keratinocytes, and its knockout disrupts this pathway, leading to abnormal accumulation of p62 and subsequent NF-κB activation 1. This disruption results in upregulation of IL-1 signaling and overexpression of IL-36α, a critical mediator of skin inflammation 1. Mutations in AP1S3 are associated with generalized pustular psoriasis (GPP), an autoinflammatory skin disorder characterized by sterile pustules and systemic inflammation 23. The gene has also been implicated in cancer progression, where it enhances tumor cell proliferation and migration by activating the PI3K/AKT/mTOR pathway and modulating lipid metabolism 45. These findings establish AP1S3 as a crucial regulator of keratinocyte autophagy and skin immunity, with therapeutic implications for autoinflammatory disorders and cancer treatment.