Physiological functions of CKIP-1: From molecular mechanisms to therapy implications.

The casein kinase 2 interacting protein-1 (CKIP-1, also known as PLEKHO1) is initially identified as a specific CK2α subunit-interacting protein. Subsequently, various proteins, including CPα, PAK1, Arp2/3, HDAC1, c-Jun, ATM, Smurf1, Rpt6, Akt, IFP35, TRAF6, REGγ and CARMA1, were reported to interact with CKIP-1. Owing to the great diversity of interacted proteins, CKIP-1 exhibits multiple biologic functions in cell morphology, cell differentiation and cell apoptosis. Besides, these functions are subcellular localization, cell type, and regulatory signaling dependent. CKIP-1 is involved in biological processes consisting of bone formation, tumorigenesis and immune regulation. Importantly, deregulation of CKIP-1 results in osteoporosis, tumor, and atherosclerosis. In this review, we introduce the molecular functions, biological processes and promising of therapeutic strategies. Through summarizing the intrinsic mechanisms, we expect to open new therapeutic avenues for CKIP-1.