Hermansky-Pudlak type 2 is an autosomal recessive disorder characterized by oculocutaneous albinism, bleeding disorders, recurrent infections, and moderate/severe neutropenia. The disease is caused by mutations in the AP3B1 gene encoding for the β3A subunit of the adaptor protein 3 (AP-3) complex. Because the expression of the β3A subunit is normally ubiquitous, its deficiency leads to a precise phenotype in cells with a large number of intracellular granules, such as neutrophils, natural killer cells, cytotoxic T lymphocytes, platelets, and melanocytes. Given the AP-3 deficiency, the lysosomal membrane proteins are not appropriately sorted to the granules but are delivered to plasma membrane with subsequent effects on cell development and differentiation. Missorting of proteins (eg, tyrosinase) in melanocytes and platelets accounts for oculocutaneous albinism and bleeding disorders, respectively. Absence of AP-3 leads to low intracellular content of neutrophil elastase and consequently to neutropenia. Abnormal movement of lytic granules and reduced perforin content in cytotoxic T lymphocytes and natural killer cells account for their respective defects in cytolytic activity. It is likely that the investigation of the physiopathology of Hermansky-Pudlak type 2 syndrome will reveal nonredundant functions of this adaptor protein in the intracellular trafficking of membrane proteins. © 2007 American Academy of Allergy, Asthma & Immunology.
Badolato, R., & Parolini, S. (2007, October). Novel insights from adaptor protein 3 complex deficiency. Journal of Allergy and Clinical Immunology. https://doi.org/10.1016/j.jaci.2007.08.039