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Myosin phosphatase Rho-interacting protein (MPRIP) is a multi-domain cytoskeletal scaffold protein encoded by the MPRIP gene in humans, with a molecular weight of approximately 120 kDa. It binds to both F-actin and phosphatidylinositol 4,5-bisphosphate (PIP2), localizing to the cytoskeleton and nucleus, where it plays roles in regulating actin stress fiber formation and nuclear phase separation processes related to transcription. Functionally, MPRIP targets myosin phosphatase to actin filaments and regulates its activity in concert with the RhoA/ROCK (Rho-associated kinase) pathway, influencing cell contraction and cytoskeletal dynamics. Its interaction domains allow it to bind RhoA and myosin phosphatase regulatory subunit MYPT1, assembling signaling complexes crucial for smooth muscle and non-muscle cell function. Overexpression or depletion of MPRIP alters actin stress fibers, with effects varying between cell types (e.g., smooth muscle, neuronal cells). MPRIP has been reported to have nuclear functions, acting as a component of RNA Polymerase II complex and contributing to transcriptional regulation via phase separation in nuclear compartments. Disease associations include roles in vascular contractility defects and rare genetic disorders. There is currently no evidence of direct drug interactions targeting MPRIP, and it is not a validated drug biomarker.
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