AP5B1 encodes a subunit of the AP-5 (adaptor protein complex 5), a vesicular trafficking component involved in endosomal transport and lysosomal homeostasis 1. As part of the AP-5 complex, AP5B1 localizes to late endosomes and the Golgi apparatus, functioning in intracellular trafficking to maintain cellular homeostasis and proper lysosomal pathway functioning 1. Bi-allelic loss-of-function variants in AP5B1 cause autosomal recessive hereditary macular dystrophy, particularly affecting the retinal pigment epithelium (RPE)—a tissue with intense lysosomal and phagocytic activity 1. Beyond retinal disease, AP5B1 variants associate with immune-related conditions: genome-wide studies identify AP5B1 as a susceptibility locus for psoriasis 2, the atopic march (eczema progressing to asthma) 3, and asthma risk through pleiotropic effects on IgG N-glycosylation 4. AP5B1 functions as a key driver in FcγR-mediated phagocytosis and Toll-like receptor signaling pathways, with bidirectional interactions with neutrophil abundance associated with peanut allergy reaction thresholds 5. Preliminary evidence suggests AP5B1 variants may predispose to diabetic kidney disease in diabetic retinopathy patients 6 and possibly pediatric sarcoidosis 7. The gene's broad involvement in vesicular trafficking and immune regulation explains its pleiotropic disease associations.