S100PBP (S100P binding protein) functions as a tumor suppressor gene that binds to S100P in a calcium-dependent manner and regulates cellular adhesion and motility 1. The protein localizes to the nucleus and nuclear speckles, where it forms complexes with S100P, p53, and ubiquitin proteins 2. In pancreatic cancer, S100PBP expression progressively decreases during tumor progression, and its loss leads to oncogenic transformation through alterations in genes controlling cytoskeleton dynamics, cell motility, and survival 2. Mechanistically, S100PBP regulates cellular adhesion by controlling cathepsin Z protease levels, which interacts with αvβ5 integrins to mediate adhesive properties 1. The protein is regulated epigenetically by mutated KRAS, which decreases S100PBP levels, while HDAC inhibitors can rescue its expression 2. S100PBP serves as a direct target of miR-944 in cervical cancer, where its downregulation promotes cell proliferation, migration, and invasion 3. Clinically, low S100PBP expression combined with high S100P levels correlates with poor prognosis in pancreatic cancer patients 2, and S100PBP expression is associated with patient survival outcomes in breast cancer 4. DNA methylation changes in S100PBP are also linked to acute myeloid leukemia recurrence 5.