This mini-review offers an update on the rare autoimmune polyendocrinopathy syndrome (AP) with a synopsis of recent developments.Systematic search for studies related to pathogenesis, immunogenetics, screening, diagnosis, clinical spectrum, and epidemiology of AP.AP (orphan code ORPHA 282196) is defined as the autoimmune-induced failure of at least two glands. AP is divided into the rare juvenile type I and the adult types II to IV. The prevalence is 1:100.000 and 1:20.000 for types I and II-IV, respectively. While type I (ORPHA 3453) is a monogenetic syndrome with an autosomal recessive transmission related to mutations in the AIRE gene, types II-IV are genetically complex multifactorial syndromes that are strongly associated with certain alleles of the human leucocyte antigen (HLA) genes within the major histocompatibility complex located on chromosome 6, as well as the cytotoxic T-lymphocyte antigen 4 and the protein tyrosine phosphatase non-receptor type 22 gene. Addison's disease is the major endocrine component of type II (ORPHA 3143), while the coexistence of type 1 diabetes and autoimmune thyroid disease is characteristic for type III (ORPHA 227982). Genetic screening for the AIRE gene is useful in patients with suspected type I while serological screening (i.e. diabetes/adrenal antibodies) is required in patients with monoglandular autoimmunity and suspected AP. If positive, functional endocrine testing of the antibody positive patients as well as serological screening of their first-degree relatives is recommended.Timely diagnosis, genetic counseling, and optimal long-term management of AP is best offered in specialized centers.