KIDINS220 is a multifunctional scaffold protein that serves as a critical regulator of phosphate homeostasis and neurotrophin signaling. Its primary function involves forming a complex with the phosphate exporter XPR1, where KIDINS220 stabilizes XPR1 in a closed conformation and regulates its cellular localization and activity 1. The XPR1-KIDINS220 complex works synergistically with inositol pyrophosphates to control phosphate efflux, with KIDINS220 acting as a safeguard mechanism that prevents uncontrolled phosphate export 23. Mechanistically, KIDINS220 promotes sustained MAP-kinase signaling by neurotrophins through Rap1-dependent pathways and serves as a docking site for various signaling complexes involved in neuronal differentiation and survival 4. The protein also regulates cellular metabolism, as decreased KIDINS220 expression inhibits AMPK phosphorylation and reduces glycolysis in nucleus pulposus cells under mechanical stress 5. Disease relevance is significant, as heterozygous pathogenic variants cause SINO syndrome (spastic paraplegia, intellectual disability, nystagmus, and obesity), with truncated proteins showing mislocalization and trans-dominant negative effects 6. Additionally, KIDINS220 accumulates with tau in Alzheimer's disease, where GSK3β/PP1 imbalance affects its calpain processing 7. Clinically, the XPR1-KIDINS220 complex represents a therapeutic vulnerability in ovarian cancer due to phosphate dysregulation 1.