PDZD2 (PDZ domain containing 2) is a multi-PDZ domain protein that functions as both an intracellular signaling molecule and secreted factor regulating cell proliferation and differentiation. The protein is primarily localized to the endoplasmic reticulum and undergoes caspase-3-dependent proteolytic processing to generate a secreted form (sPDZD2) containing two PDZ domains 1. In pancreatic beta cells, PDZD2 is highly expressed and sPDZD2 acts as a concentration-dependent mitogen, promoting proliferation while inhibiting differentiation of pancreatic progenitor cells 23. This dual function suggests PDZD2 plays important roles in pancreatic beta-cell mass regulation and insulin production 4. In cancer contexts, PDZD2 demonstrates oncogenic properties, being upregulated in osteosarcoma where it promotes cell proliferation, migration, and invasion while being negatively regulated by tumor suppressor miR-363 5. Additionally, PDZD2 expression is stabilized by circular RNAs in lung adenocarcinoma, contributing to tumor progression 6. The protein has also been implicated in congenital heart defects, with genetic variations identified in Tetralogy of Fallot patients 7. PDZD2's multiple PDZ domains enable diverse protein interactions that mediate these various cellular functions across different tissue contexts.