Olfm4, or olfactomedin 4, is a glycoprotein-encoding gene. It plays diverse roles in multiple biological processes and is associated with several signaling pathways. For instance, it may be involved in the NF-κB, Wnt, and Hippo signaling pathways, which are crucial for regulating inflammation, cell proliferation, and tumorigenesis [1,2,4]. Genetic models, such as knockout (KO) mouse models, have been essential in understanding its functions.

In KO mouse models, OLFM4-deficient mice show distinct phenotypes. In intestinal inflammation, OLFM4 -/- mice are more susceptible to bacterial infection but more resistant to anti-CD40 induced innate colitis, with impaired IL-22 production by ILC3, indicating its role in modulating intestinal inflammation [3]. In the progression from colitis to colorectal cancer, myeloid cell-specific OLFM4-deficient mice have poor recruitment of PMN-MDSCs, impaired intestinal homeostasis, and delayed disease development, suggesting its significance in this process [5]. Female mice lacking Olfm4 in myeloid cells experience fetal growth restriction during pregnancy, and their offspring exhibit intestinal inflammation, highlighting its role in fetal development and neonatal gut inflammation [6]. In a pediatric murine sepsis model, OLFM4-null pups have increased survival, reduced renal cell apoptosis, and lower plasma creatinine, indicating a negative impact of OLFM4 on sepsis outcomes [7].

In conclusion, Olfm4 is a multifunctional gene involved in various biological processes and diseases. KO mouse models have revealed its roles in intestinal inflammation, colitis-associated tumorigenesis, fetal development, neonatal gut inflammation, and sepsis. Understanding Olfm4's functions through these models provides valuable insights into the mechanisms of these diseases and potential therapeutic targets.