TENT5C (terminal nucleotidyltransferase 5C) is a noncanonical poly(A) polymerase that functions as a tumor suppressor and secretory pathway regulator 1. As a member of the TENT5 family, TENT5C selectively stabilizes mRNAs encoding endoplasmic reticulum-imported proteins, thereby promoting expression of secretory cargo and proteins involved in protein folding and trafficking 1. TENT5C likely functions together with its paralog TENT5A in regulating cytoplasmic polyadenylation of secreted proteins during bone formation 2. Mechanistically, TENT5C acts as a corepressor in ligand-bound glucocorticoid receptor and estrogen receptor α complexes, with its third LXXLL motif directly interacting with estrogen receptor α 3. Additionally, TENT5C localizes to centrioles and inhibits Polo-like kinase 4 activity independent of its nucleotidyl transferase function, thereby suppressing centriole duplication and cancer cell invasion 4. Clinically, TENT5C is frequently mutated or deleted in multiple myeloma patients, where loss-of-function mutations confer selective advantage to malignant plasma cells by reducing secretory capacity 5. Loss of TENT5C is also documented in advanced colorectal cancer 4. Conversely, TENT5C expression sensitizes myeloma cells to sphingosine kinase 1 inhibition, suggesting therapeutic potential 6. In neuroinflammation, TENT5C downregulation mediates neuroprotective anti-inflammatory effects of mild hypothermia 7.