Phosphorylation of myosin II is important in many aspects of cell function and involves a myosin kinase, e.g. myosin light chain kinase, and a myosin phosphatase (NIP). MP is regulated by the myosin phosphatase target subunit (MYPT1). The domain structure, properties, and genetic analyses of MYPT1 and its isoforms are outlined. MYPT1 binds the catalytic subunit of type I phosphatase, 6 isoform, and also acts as an interactive platform for many other proteins. A key reaction for NIP is with phosphorylated myosin II and the first process shown to be regulated by NIP was contractile activity of smooth muscle. In cell division and cell migration myosin II phosphorylation also plays a critical role and these are discussed. However, based on the wide range of partners for MYPT1 it is likely that MP is implicated with substrates other than myosin II. Open questions are whether the diverse functions of NIP reflect different cellular locations and/or specific roles for the MYPT1 isoforms. (c) 2007 Elsevier Inc. All rights reserved.