MPP3 (MAGUK p55 scaffold protein 3) is a membrane-associated guanylate kinase protein that functions as a scaffolding molecule organizing protein complexes at cell-cell junctions and the plasma membrane. At the molecular level, MPP3 participates in cell spreading through the phosphoinositide-3-kinase (PI3K) pathway by connecting CADM1 to DLG1 and the PI3K regulatory subunit 1. MPP3 stabilizes the serotonin 5-HT2C receptor at the plasma membrane and prevents its desensitization, opposing PSD-95's effects 2. The protein regulates trafficking and processing of nectins, cell-cell adhesion molecules, in an isoform-specific manner, increasing cell surface expression of nectin-1α and nectin-3α 3. In retinal tissue, MPP3 localizes at photoreceptor synapses and adherens junctions, colocalizing with MPP5 and CRB1 at the outer limiting membrane, implicating it in photoreceptor polarity maintenance 4. Clinically, MPP3 acts as a putative tumor suppressor; its expression is frequently lost in colorectal carcinomas and non-small cell lung cancers through promoter hypermethylation 5, 6. Additionally, downregulation of MPP3 expression via extracellular vesicle-mediated MIR22HG transfer impairs enteric neural crest cell colonization in Hirschsprung's disease 7. These findings suggest MPP3 is essential for maintaining tissue organization and preventing malignant transformation.