CDK5RAP3, also known as C53 and LZAP, was originally identified as a binding protein of Cdk5 activator p35. It is involved in multiple biological functions such as cell proliferation, apoptosis, invasion, and metastasis, and is associated with pathways like UFMylation, mTOR, and Akt/GSK-3β/Wnt/β -catenin. Genetic models, especially KO/CKO mouse models, have been crucial in understanding its functions [1,2,3,4,5,6,7,8,9,10].

Cdk5rap3 knockout mice showed prenatal lethality with severe liver hypoplasia, indicating its importance in liver development [2]. Hepatocyte-specific Cdk5rap3 knockout mice suffered post-weaning lethality due to hypoglycemia and impaired lipid metabolism [2]. In the intestine, IEC-specific deletion of Cdk5rap3 led to nearly complete loss of Paneth cells and increased colitis susceptibility [4]. In breast cancer, low CDK5RAP3 tumor expression was associated with poor survival, and in gastric cancer, it acts as a tumour suppressor by regulating TAM infiltration and polarization [5,7].

In conclusion, CDK5RAP3 is essential for various biological processes including liver development, Paneth cell maintenance, and is involved in multiple disease conditions such as cancer. The use of KO/CKO mouse models has significantly enhanced our understanding of its role in these biological processes and disease areas, providing potential targets for therapeutic interventions.