S100A14 is a calcium-binding protein that plays context-dependent roles in cell proliferation, apoptosis, and migration through interactions with multiple signaling molecules. While structurally containing two EF-hand calcium-binding domains 1, S100A14 does not bind calcium according to functional studies. S100A14 regulates cell survival by modulating p53/TP53 protein levels and influences cell migration through transcriptional control of matrix metalloproteinases (MMP1, MMP9, MMP13) 2. The protein interacts with S100A16, regulating its protein stability through post-transcriptional mechanisms independent of proteasomal/lysosomal degradation 3. In cancer, S100A14 exhibits tissue-specific functions: elevated expression associates with poor overall survival in breast and ovarian cancers 4, and promotes cervical cancer progression via epithelial-mesenchymal transition (EMT) 5. However, in colorectal cancer, S100A14 acts as a tumor suppressor when stabilized via Mfsd2a-mediated interaction, suppressing STAT3 phosphorylation and metastasis 6. In hepatocellular carcinoma, S100A14 confers sorafenib resistance by stabilizing glutaminase and reducing oxidative stress 7. These findings suggest S100A14 serves as a prognostic biomarker and potential therapeutic target, with its function largely dependent on tissue context and interacting protein partners.