Pcbp2, also known as Poly (rC)-binding protein 2, is an RNA-binding protein and a cytosolic Fe(II) chaperone. It plays crucial roles in various biological processes, regulating mRNA metabolism, intracellular iron transport, and antiviral signaling. It is associated with pathways like cGAS-STING and is important for maintaining normal cell functions and responding to different physiological and pathological challenges. Genetic models, such as KO mouse models, are valuable for studying its functions.

In pancreatic β cells, Pcbp2-deficient mice showed defects in insulin secretion-related mechanisms like calcium flux, insulin granule ultrastructure and exocytosis, indicating its requirement for β cell function and adaptation to glucose [1]. In malignant mesothelioma cells, knockdown of Pcbp2 decreased TfR1 and FTH expression, inhibited cell proliferation, and increased sensitivity to ferroptosis, suggesting its role in ferroptosis-resistance during carcinogenesis [2]. In glioma, Pcbp2 promoted tumor progression, reduced oxidative stress-induced apoptosis by suppressing the cGAS/STING pathway, and its stability was increased by METTL3-mediated m6A modification [3]. In breast cancer, non-full-length 3'UTR PCBP2 transcripts enhanced oncogenic and metastatic capacities, and PCBP2 promoted cancer cell oncogenicity by upregulating UFD1 and NT5E [4]. In prostate cancer, PCBP2 promoted cell proliferation, migration, and invasion by inhibiting the cGAS-STING pathway, and was identified as a key risk factor associated with poor prognosis [5].

In conclusion, Pcbp2 is essential for maintaining normal cell functions in multiple cell types. Its functions range from regulating glucose-adaptive gene programs in pancreatic β cells to influencing ferroptosis-resistance in cancer cells. The use of Pcbp2 KO/CKO mouse models has significantly contributed to understanding its roles in diseases such as type 2 diabetes, various cancers, and potentially ferroptosis-related pathologies.