Cpne1, a calcium-dependent, phospholipid-binding protein, is ubiquitously expressed in various tissues and organs. It participates in multiple biological processes, such as cell proliferation, apoptosis, differentiation, and is associated with pathways like MAPK, PERK-eIF2α, PI3K/AKT/HIF-1α, and MET signaling pathways [1,2,6,8]. Genetic models, especially KO mouse models, are valuable for studying its functions.

In gastric, pancreatic, non-small cell lung, breast, and hepatocellular carcinomas, Cpne1 silencing inhibits cell proliferation, induces apoptosis, and arrests the cell cycle. For example, in gastric cancer, Cpne1 knockdown inhibits tumor growth in vivo and in vitro by deactivating the DDIT3-FOS-MKNK2 axis of the MAPK pathway [1]. In pancreatic cancer, silencing the Cpne1-TRAF2 axis restrains cancer development [3]. In non-small cell lung cancer, Cpne1 promotes tumorigenesis by interacting with RACK1 and activating the MET signaling pathway [6]. In breast cancer, Cpne1 mediates glycolysis and metastasis through the PI3K/AKT/HIF-1α signaling pathway [8]. In hepatocellular carcinoma, knockdown of Cpne1 inhibits the AKT/P53 pathway, reducing cell proliferation, migration, and invasion [9]. In sarcopenia, Cpne1 overexpression in young muscles disrupts mitochondrial function and myogenesis via the PERK-eIF2α pathway [2]. In tooth germ development, Cpne1 is involved in odontoblastic differentiation of stem cells from apical papilla related to the AKT signaling pathway [7]. In neurons, HAX1 binds to Cpne1 to negatively affect Cpne1-mediated neuronal differentiation [4]. In sperm, Cpne1 deficiency preserves sperm motility under Ca2+ channel blockade [5].

In conclusion, Cpne1 plays crucial roles in cell-related biological processes and is significantly involved in multiple diseases, especially various cancers. The use of Cpne1 KO/CKO mouse models has revealed its role in promoting cancer progression and its association with disease-related pathways, providing potential therapeutic targets for these diseases.