ANXA10 is a calcium-dependent phospholipid-binding protein with complex, context-dependent roles in cancer biology. 1 In colorectal cancer (CRC), ANXA10 overexpression promotes progression and is associated with poor prognosis, particularly in BRAF-mutant tumors; mechanistically, ANXA10 suppresses ferroptosis by inhibiting autophagy-mediated transferrin receptor degradation. 2 ANXA10 exhibits stomach-specific expression and serves as a CreERT2 driver for generating mouse models of distinct gastric cancer subtypes. 3 In melanoma, ANXA10 similarly promotes metastasis by suppressing PKD1 degradation through TRIM41 inhibition, thereby suppressing the epithelial phenotype. Conversely, in hepatocellular carcinoma (HCC) and urothelial carcinoma (UC), ANXA10 functions as a tumor suppressor. 4 ANXA10 is downregulated in HCC and predicts better survival; its upregulation inhibits cell proliferation and migration. 5 In UC, ANXA10 positivity correlates with lower grade/stage and better survival, with expression decreasing during progression. 6 In microsatellite instability-high CRC, ANXA10 sensitizes tumors to anti-PD-1 immunotherapy by promoting HLA-DR dimer assembly through CD74 upregulation. 7 In pancreatic β-cells, ANXA10 responds to metabolic stress-induced calcium influx but suppresses glucose-stimulated calcium elevation and insulin secretion, contributing to diabetes progression. These findings establish ANXA10 as a multifunctional regulator with cancer type- and context-specific effects.