CRELD1, or Cysteine-Rich with EGF-Like Domains 1, is a gene with crucial functions. It acts as a regulator of the calcineurin/NFATc1 signaling pathway, which is important for cardiac development and T cell-related biological processes [4,5]. Mutations in CRELD1 are associated with various human diseases, highlighting its overall biological importance. Genetic models, such as knockout (KO) mice, have been valuable in studying its functions.

In KO mouse models, lack of myocardial Creld1 causes extracellular matrix remodeling and trabeculation defects by modulating the Notch1 signaling pathway, leading to early postnatal death due to myocardial hypoplasia, revealing its role in cardiac maturation and function [2]. In T cell-specific Creld1-deficient mice, loss of Creld1 is associated with overactivation and increased apoptosis of T cells, resulting in a net loss of T cells with age, indicating its role in immune system homeostasis [3]. Xenopus tropicalis with creld1 knockdown display developmental defects and increased seizure susceptibility, while missense variants in human CRELD1 lead to reduced protein function [1].

In conclusion, CRELD1 is essential for heart development, regulating cardiac maturation and function, and also plays a key role in immune system homeostasis, especially in T cell regulation. The use of KO and other genetic models has significantly contributed to understanding its functions in these disease-related biological processes, such as cardiac disorders and immune-related conditions [1,2,3].