Tent5c, also known as FAM46C, is a non-canonical cytoplasmic poly(A) polymerase. It has diverse functions, including regulating the polyadenylation of mRNAs encoding secreted proteins, and is involved in important biological processes such as gametogenesis, the humoral immune response, and acts as a potential tumor suppressor [3,4,6]. It may also be associated with immune and inflammatory responses regulation [2,5]. Genetic models, especially mouse models, are crucial for studying its functions.

In mouse models, Tent5c knockout reveals its essential role in gametogenesis. Tent5c and Tent5d regulate different stages of spermatogenesis, with male sterility occurring upon knockout of either gene. In oogenesis, Tent5b and Tent5c play redundant roles, and double knockout leads to oocyte degeneration [3]. In the humoral immune response, Tent5c-/-mice produce fewer antibodies and have a diminished T-cell-independent immune response, despite having more CD138high plasma cells due to accelerated differentiation. B cells from these mice also have an impaired secretory pathway [4]. In cancer, loss of FAM46C occurs in patient-derived colorectal cancer tumor tissue, and its depletion in gastric adenocarcinoma portends cancer recurrence and death [1,7].

In conclusion, Tent5c is essential for gametogenesis and the humoral immune response. Its role as a potential tumor suppressor is emerging, especially in colorectal and gastric cancers. The gene knockout mouse models have been instrumental in revealing these functions, providing valuable insights into the biological processes and disease mechanisms related to Tent5c.