MPRIP (myosin phosphatase Rho interacting protein) is a multifunctional F-actin-binding scaffold protein that regulates cytoskeletal organization and transcription. Primarily, MPRIP targets myosin phosphatase to the actin cytoskeleton and is required for RhoA/ROCK1-mediated regulation of actin dynamics 1. Its depletion increases stress fiber stabilization in smooth muscle cells through elevated myosin phosphorylation 1, while overexpression promotes stress fiber disassembly 1. Beyond cytoskeletal functions, MPRIP participates in gene regulation by recruiting tyrosine1-phosphorylated RNA polymerase II CTD to nuclear PIP2-rich structures, modulating RNAPII transcription and condensation 23. MPRIP also mediates leukocyte migration through lysosomal calcium-dependent interaction with the Ragulator complex, which activates myosin IIA 4. Clinically, MPRIP dysregulation is implicated in pancreatic cancer metastasis, where RBFOX2-regulated MPRIP splicing modulates cytoskeletal organization and focal adhesion formation 1. Additionally, germline MPRIP mutations are associated with non-traumatic osteonecrosis of the femoral head through intravascular coagulation dysfunction 5. During apoptosis, caspase-mediated MPRIP cleavage generates a truncated form that coordinates repetitive membrane blebbing through myosin light chain phosphorylation regulation 6.