Polycystic ovary syndrome (PCOS) is a complicated reproductive endocrine disease characterized by hyperandrogenism, polycystic ovaries, and anovulation. Previous studies have revealed that androgen receptors (ARs) are strongly associated with hyperandrogenism and abnormalities in folliculogenesis in patients with PCOS. However, the kinases responsible for androgen receptor activity, especially in granulosa cells, and the role of casein kinase 2 alpha (CK2 alpha) specifically in the pathogenesis of PCOS, remain unknown. Here, we show that both CK2 alpha protein and mRNA levels were higher in luteinized granulosa cells of patients with PCOS compared with non-PCOS, as well as in the ovarian tissues of mice with a dehydroepiandrosterone-induced PCOS-like phenotype, compared with controls. In addition, CK2 alpha not only interacted with AR in vivo and in vitro, but it also phosphorylated and stabilized AR, triggering AR and ovulation related genes excessive expression. CK2 alpha also promoted cell proliferation in the KGN cell line and inhibited apoptosis. Collectively, the finding highlighted that the CK2 alpha-AR axis probably caused the etiology of the PCOS. Thus, CK2 alpha might be a promising clinical therapeutic target for PCOS treatment. (C) 2020 Elsevier Inc. All rights reserved.